bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune checkpoint inhibitors-related myocarditis in patients with cancer: an analysis of international spontaneous reporting systems
Authors: Ma Rulan , Wang Quanziang , Meng Deyu , Li Kang , zhang yong
Published: November 2020

Background: Immune checkpoint inhibitors induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADRs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCNPP) method was the strongest. Conclusion: The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which are consistent with the results of previous clinical trials and can provide a reference for clinical workers when using ICIs.
Water-soluble chlorophyll-binding proteins from Brassica oleracea allow for stable photobiocatalytic oxidation of cellulose by a lytic polysaccharide monooxygenase.
Authors: Dodge N. , Russo D. A. , Blossom B.M. , Singh R.K. , Oort B. van , Croce R. , Bjerrum M. J. , Jensen Poul Erik
Published: November 2020

Background: Lytic polysaccharide monooxygenases (LPMOs) are indispensable redox enzymes used in industry for the saccharification of plant biomass. LPMO-driven cellulose oxidation can be enhanced considerably through photobiocatalysis using chlorophyll derivatives and light. Water soluble chlorophyll binding proteins (WSCPs) make it is possible to stabilize and solubilize chlorophyll in aqueous solution, allowing for in vitro studies on photostability and ROS production. Here we aim apply a WSCP-Chl α as a photosensitizing complex for photobiocatalysis with the LPMO, TtAA9. Results: We have in this study demonstrated how WSCP reconstituted with chlorophyll a (WSCP-Chl α) can create a stable photosensitizing complex which produces controlled amounts of H2O2 in the presence of ascorbic acid and light. WSCP-Chl α is highly reactive and allows for tightly controlled formation of H2O2 by regulating light intensity. TtAA9 together with WSCP-Chl α shows increased cellulose oxidation under low light conditions, and the WSCP-Chl α complex remains stable after 24 hours of light exposure. Additionally, the WSCP-Chl α complex demonstrates stability over a range of temperatures and pH conditions relevant for enzyme activity in industrial settings.Conclusion: With WSCP-Chl α as the photosensitizer, the need to replenish Chl is greatly reduced, enhancing the catalytic lifetime of light-driven LPMOs and increasing the efficiency of cellulose depolymerization. WSCP-Chl α allows for stable photobiocatalysis providing a sustainable solution for biomass processing.
Sheep nemabiome diversity and its response to anthelmintic treatment in Swedish sheep herds
Authors: Halvarsson Peter , Höglund Johan
Published: November 2020

BackgroundA novel way to study the species composition and diversity of nematode parasites in livestock is to perform deep sequencing on composite samples containing a mixture of different species. Herein we describe for the first-time the nematode community structure (nemabiome) inhabiting Swedish sheep and how these are/were affected by host age and recent anthelmintic treatments.MethodsA total of 158 fecal samples were collected (n=35 in 2007 and n=123 in 2013-2016) and cultured from groups of sheep on 61 commercial farms in the south-central part of country where most animals are grazed. Among the samples, 2 x 44 (56%) were paired collections from the same groups pre- and post-treatment with macrocyclic lactones, benzimidazoles or levamisole. The sequences were analyzed for their nemabiome using the PacBio platform followed by bioinformatic sequence analysis with SCATA. Species richness and diversity were calculated and analyzed in R.ResultsNematode ITS2 sequences were found in all larval culture samples except two, even though the fecal egg counts were below the McMaster threshold in 20 samples. Sequencing yielded, on average, 1,008 sequences per sample. In total 16 operational taxonomical units (OTU), all had ≥98 % identity to sequences in the NCBI database, were recognized. The OTUs found represented nematode species of which 10 are commonly associated with sheep. Multiple species were identified in all pre anthelmintic treatment larval culture samples. No effects on nematode diversity were found in relation to host age. On the other hand, recent anthelmintic treatment lowered species richness, especially after use of ivermectin and albendazol. Interestingly, despite zero egg counts after use of levamisole, these samples still contained nematode DNA and especially H. contortus.ConclusionsOur findings provide evidence that nemabiome analysis combined with diversity index analysis provide a sensitive and objective methodology in the study of the efficacy of anthelmintic treatment, as both high and low abundant species were detected.
Predicting COVID-19 Disease Progression and Patient Outcomes based on Temporal Deep Learning
Authors: Sun Chenxi , Hong Shenda , Song Moxian , Li Hongyan , Wang Zhenjie
Published: November 2020

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused health concerns worldwide since December 2019. From the beginning of infection, patients will progress through different symptom stages, such as fever, dyspnea or even death. Identifying disease progression and predicting patient outcome at an early stage helps target treatment and resource allocation. However, there is no clear COVID-19 stage definition, and few studies have addressed characterizing COVID-19 progression, making the need for this study evident.Methods: We proposed a temporal deep learning method, based on a time-aware long short-term memory (T-LSTM) neural network and used an online open dataset, including blood samples of 485 patients from Wuhan, China, to train the model. Our method can grasp the dynamic relations in irregularly sampled time series, which is ignored by existing works. Specifically, our method predicted the outcome of COVID-19 patients by considering both the biomarkers and the irregular time intervals. Then, we used the patient representations, extracted from T-LSTM units, to subtype the patient stages and describe the disease progression of COVID-19.Results: Using our method, the accuracy of the outcome of prediction results was more than 90% at 12 days and 98%, 95% and 93% at 3, 6, and 9 days, respectively. Most importantly, we found 4 stages of COVID-19 progression with different patient statuses and mortality risks. We ranked 40 biomarkers related to disease and gave the reference values of them for each stage. Top 5 is Lymph, LDH, hs-CRP, Indirect Bilirubin, Creatinine. Besides, we have found 3 complications - myocardial injury, liver function injury and renal function injury. Predicting which of the 4 stages the patient is currently in can help doctors better assess and cure the patient.Conclusions: To combat the COVID-19 epidemic, this paper aims to help clinicians better assess and treat infected patients, provide relevant researchers with potential disease progression patterns, and enable more effective use of medical resources. Our method predicted patient outcomes with high accuracy and identified a four-stage disease progression. We hope that the obtained results and patterns will aid in fighting the disease.
Expectations and Experiences with Physician Care among Patients Receiving Post-Acute Care in US Skilled Nursing Facilities
Authors: Ryskina Kira L , Foley Kierra A. , Karlawish Jason H. , Uy Joshua D. , Lott Briana , Goldberg Erica , Hodgson Nancy A.
Published: November 2020

Background: In the US, post-acute care in skilled nursing facilities (SNFs) is common and outcomes vary greatly across facilities. Little is known about the expectations of patients and their caregivers about physician care during the hospital to SNF transition. Our objectives were to (1) describe the experiences and expectations of patients and their caregivers with SNF physicians in SNFs, and (2) identify patterns that differed between patients with vs. without cognitive impairment.Methods: This qualitative study used grounded theory approach to analyze data collected from semi-structured interviews at five SNFs in January-August 2018. Patients admitted for short-term SNF care 5-10 days prior were eligible to participate. Thematic analysis was performed to detect recurrent themes with a focus on modifiable aspects of physician care. Analysis was stratified by patient cognitive impairment (measured by the Montreal Cognitive Assessment at the time of the interview). Results: Fifty patients and six caregivers were interviewed. Major themes were: (1) patients had poor awareness of the physician in charge of their care; (2) they were dissatisfied with the frequency of interaction with the physician; and (3) participants valued the perception of receiving individualized care from the physician. Less cognitively impaired patients were more concerned about limited interactions with the physicians and were more likely to report attempts to seek out the physician. Conclusion: Patient and caregiver expectations of SNF physicians were not well aligned with their experiences. SNFs aiming to improve satisfaction with care may focus efforts in this area, such as facilitating frequent communication between physicians, patients and caregivers.
Suppressor of Variegation 3-9 Homologue 1 Impairment and Neutrophil-skewed Systemic Inflammation Are Associated with Comorbidities in COPD
Authors: Chen Tzu-Tao , Wu Sheng-Ming , Chen Kuan-Yuan , Tseng Chien-Hua , Ho Shu-Chuan , Chuang Hsiao-Chi , Feng Po-Hao , Liu Wen-Te , Han Chia-Li , Huang Erick Wan-Chun , Yeh Yun-Kai , Lee Kang-Yun
Published: November 2020

BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD.METHODS: To assess whether impaired SUV39H1 expression in COPD patients leads to neutrophilic inflammation, downstream responses to IL-8 and suppression of Th2 responses, the SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy subjects and 30 COPD patients were measured by immunoblotting. Clinical outcomes associated with SUV39H1-related inflammation were also studied. The relationships between SUV39H1 and neutrophil or eosinophil (Th2 response) counts and clinical outcomes were evaluated. In an extended COPD cohort (213 patients), association analyses of blood cell counts with comorbidities and exacerbations were performed.RESULTS: Low SUV39H1 expression was associated with high neutrophil counts and a trend towards low eosinophil counts. In the extended cohort, the high comorbidity group had higher neutrophil counts than the low comorbidity group but similar whole white blood cell counts. The eosinophil percentage and eosinophil/neutrophil ratio displayed contrasting results. The proportion of neutrophils was correlated with COPD comorbidities. Patients with 0-1 moderate to severe exacerbations in the past year had numbers of neutrophils and eosinophils similar to those of patients who experienced more than an exacerbation. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities.CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.
Exploring the effectiveness of a COVID-19 contact tracing app with an agent-based model
Authors: Almagor Jonatan , Picascia Stefano
Published: November 2020

A contact-tracing strategy has been deemed necessary to contain the spread of COVID-19 following the relaxation of lockdown measures. Using an agent-based model, we explore one of the technology-based strategies proposed, a contact-tracing smartphone app. The model simulates the spread of COVID-19 in a population of agents on an urban scale. Agents are heterogeneous in their characteristics and are linked in a multi-layered network representing the social structure - including households, friendships, employment and schools. We explore the interplay of various adoption rates of the contact-tracing app, different levels of testing capacity, and behavioural factors to assess the impact on the epidemic. Results suggest that a contact tracing app can contribute substantially to reducing infection rates in the population when accompanied by a sufficient testing capacity or when the testing policy prioritises symptomatic cases. As user rate increases, prevalence of infection decreases. With that, when symptomatic cases are not prioritised for testing, a high rate of app users can generate an extensive increase in the demand for testing, which, if not met with adequate supply, may render the app counterproductive. This points to the crucial role of an efficient testing policy and the necessity to upscale testing capacity.
Clean energy utilization technology in the transformation of urban existing residence in China
Authors: Zhao Li , Chen Wei , Li Qiong , Wu WeiWei
Published: November 2020

Clean energy substitution technology of existing residential buildings in cities is an inevitable choice for sustainable development and low-carbon ecological city construction. In this paper, the current status of energy-saving renovation and renewable energy application of existing residential buildings in various cities in China is summarized by using statistical method. The geographical distribution of clean energy power generation in primary energy production has been deeply explored in China. According to different climatic division of urban existing residence, the clean energy production and consumption are analyzed and predicted based on STIRPAT model. The results shows that the energy consumption of urban residential buildings in 2016 has increases by 43.6% compared with 2009. Clean energy has also increased from 7.9% to 13.4%. Different climate regions have different advantages in clean energy. Nuclear power generation is ahead of other regions in hot summer and warm winter regions, and wind power and solar power generation are strong in severe cold and cold regions. The results can provide basic data support for planning and implementation of clean energy upgrading and transformation system in urban existing residences in China.
Population Genetic Analysis of Plasmodium falciparum Circumsporozoite Protein in Two Distinct Ecological Regions in Ghana
Authors: Amegashie Elikplim A , Amenga-Etego Lucas , Adobor Courage , Ogoti Peter , Mbogo Kevin , Amambua-Ngwa Alfred , Ghansah Anita
Published: November 2020

BackgroundExtensive genetic diversity in the Plasmodium falciparum circumsporozoite protein (PfCSP) is a major contributing factor to the moderate efficacy of the RTS,S/AS01 vaccine. Transmission intensity and the rates of recombination within and between populations influence the extent of genetic diversity. Understanding the extent and dynamics of PfCSP genetic diversity in different transmission settings will help to interpret the results of current RTS,S efficacy and Phase IV implementation trials conducted within and between populations in malaria endemic areas such as Ghana. MethodsPfcsp sequences were retrieved from Illumina generated paired-end short-read sequences of 101 and 131 malaria samples from children aged 6-59 months with clinical malaria presenting at health facilities in Cape Coast (on the coastal belt) and Navrongo (Guinea savannah region) respectively in Ghana. The sequences were mapped onto the 3D7 reference strain genome to yield high-quality genome-wide coding sequence data. Following data filtering and quality checks to remove missing data, 220 sequences were retained and analyzed for allele frequency spectrum, genetic diversity both within host and between the populations and signatures of selection. Population genetics tools were used to determine the extent and dynamics of Pfcsp diversity in P. falciparum from the two geographically distinct locations in Ghana. ResultsPfcsp was extensively diverse at the two sites with the higher transmission site, Navrongo, recording both higher within host and population level diversity. The vaccine strain C-terminal epitope of Pfcsp was found in only 5.9% and 45.7% of the Navrongo and Cape Coast sequences respectively. Amino acid variations ranging between 1 and 6 were observed in the TH2R and TH3R epitope regions of the PfCSP. Tajima’s D was negatively skewed especially for the population from Cape Coast given expected historical population expansion. On the contrary, positive Tajima’s D was observed for the Navrongo P. falciparum population, consistent with balancing selection acting on the immuno-dominant TH2R and TH3R vaccine epitopes. ConclusionThe low frequencies of Pfcsp vaccine haplotype in the populations analyzed calls for additional molecular and immuno-epidemiological studies with temporal and wider geographic sampling in endemic populations targeted for RTS,S application. These results have implications on the efficacy of the vaccine in Ghana and will inform the choice of alleles to include in future multivalent or chimeric vaccines.
Increasing newly diagnosed inflammatory bowel disease and improving prognosis in China: a 30-year retrospective study from a single centre
Authors: Lv Hong , Jin Meng , Zhang Huimin , Chen Xuanfu , Wu Meixu , Guo Mingyue , Zhou Runing , Wang Zheng , Yang Hong , Qian Jiaming
Published: November 2020

Background: We aimed to characterize the trends of prognosis in ulcerative colitis (UC) and Crohn’s disease (CD) in a Chinese tertiary hospital. Methods: A 30-year retrospective cohort analysis was conducted at Peking Union Medical College Hospital. Consecutive patients newly diagnosed with UC or CD from 1985 to 2014 were included. The primary outcome was in-hospital mortality. The secondary outcomes included surgery and length of stay in hospital. The Pearson correlation coefficient was applied to determine the relationship between time and prognosis. Multivariable logistic regression analysis was performed to determine the risk factors for in-hospital mortality and surgery. Results: In total, 1467 patients were included in this study (898 cases with UC and 569 cases with CD). Annual admissions for UC and CD have increased significantly over the last 30 years (UC, r=0.918, P<0.05; CD, r=0.898, P<0.05). Decreased in-hospital mortality was observed both in patients with UC and CD (UC, from 2.44% to 0.27%, r=-0.827, P<0.05; CD, from 12.50% to 0.00%, r=-0.978, P<0.05). A decreasing surgery rate was observed in patients with CD (r=-0.847, P<0.05), while an increasing surgery rate was observed in patients with UC (r=0.956, P<0.05). Shortened average lengths of hospital stay were observed in both UC and CD patients (UC, from 47.83±34.35 days to 23.58±20.05 days, r=-0.970, P<0.05; CD, from 65.50±50.57 days to 26.41±18.43 days, r=-0.913, P<0.05). Toxic megacolon and septic shock were independent risk factors for in-hospital mortality in patients with UC. Intestinal fistula and intestinal perforation were independent risk factors for in-hospital mortality in patients with CD. Conclusions: In this cohort, the admissions of patients with UC and CD were increased, with significantly improved prognoses during the past 30 years.
Spatial-temporal patterns of malaria incidence in Uganda using HMIS data from 2015 to 2019
Authors: Kigozi Simon , Kigozi Ruth N , Sebuguzi Catherine M , Cano Jorge , Rutazaana Damian , Opigo Jimmy , Bousema Teun , Yeka Adoke , Gasasira Anne , Sartorius Benn , Pullan Rachel L
Published: November 2020

Background. As global progress to reduce malaria transmission continues, it is increasingly important to track changes in malaria incidence rather than prevalence. Risk estimates for Africa have largely underutilized available health management information systems (HMIS) data to monitor trends. This study uses national HMIS data together with environmental and geographical data, to assess spatial-temporal patterns of malaria incidence at facility catchment level in Uganda over a recent 5-year period.Methods. Data reported by 3446 health facilities in Uganda, between July 2015 and September 2019 was analysed. To assess the geographic accessibility of the health facilities network, AccessMod was employed to determine a three-hour cost-distance catchment around each facility. Using confirmed malaria cases and total catchment population by facility, an ecological Bayesian conditional autoregressive spatial-temporal Poisson model was fitted to generate monthly posterior incidence rate estimates, adjusted for caregiver education, rainfall, land surface temperature, night-time light (an indicator of urbanicity), and vegetation index.Results. An estimated 38.8 million (95% Credible Interval [CI]: 37.9 – 40.9) confirmed cases of malaria occurred over the period, with a national mean monthly incidence rate of 20.4 (95% CI: 19.9 - 21.5) cases per 1000, ranging from 8.9 (95% CI: 8.7 – 9.4) to 36.6 (95% CI: 35.7 – 38.5) across the study period. Strong seasonality was observed, with June-July experiencing highest peaks and February-March the lowest peaks. There was also considerable geographic heterogeneity in incidence, with health facility catchment relative risk during peak transmission months ranging from 0 to 50.5 (95% CI: 49.0 – 50.8) times higher than national average. Both districts and health facility catchments showed significant positive spatial autocorrelation; health facility catchments had global Moran’s I = 0.3 (p<0.001) and districts Moran’s I = 0.4 (p<0.001). Notably, significant clusters of high-risk health facility catchments were concentrated in Acholi, West Nile, Karamoja, and East Central – Busoga regions.Conclusion. Findings showed clear countrywide spatial-temporal patterns with clustering of malaria risk across districts and health facility catchments within high risk regions, which can facilitate targeting of interventions to those areas at highest risk. Moreover, despite high and perennial transmission, seasonality for malaria incidence highlights the potential for optimal and timely implementation of targeted interventions.
Individual-based dengue virus surveillance in Aedes aegypti mosquitoes concurrently collected with suspected patients in Tarlac City, Philippines
Authors: Balingit Jean Claude , Carvajal Thaddeus M. , Saito-Obata Mariko , Gamboa Maribet , Nicolasora Amalea Dulcene , Sy Ava Kristy , Oshitani Hitoshi , Watanabe Kozo
Published: November 2020

Background: Vector control measures are critical in the prevention and reduction of dengue virus (DENV) transmission. In this context, an effective vector control is reliant not only on the knowledge of mosquito abundance, but also on the timely and accurate detection of mosquito infection. Mosquito-based virus surveillance programs typically rely on a pool-based mosquito testing, although whether individual-based mosquito testing could represent a feasible alternative is not largely studied. Applying an individual-based mosquito testing approach, we conducted a one-month DENV surveillance of adult Aedes (Ae.) aegypti mosquitoes around households of suspected dengue patients during the 2015 dengue peak season in Tarlac City, Philippines to more accurately assess the mosquito infection rate and identify the DENV serotypes and genotypes concurrently co-circulating in mosquitoes and patients.Methods: We performed a one-step multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for the simultaneous DENV detection and serotyping in patients and individual female Ae. aegypti mosquito. Additionally, we performed sequencing and phylogenetic analyses to further characterize the detected DENVs in mosquitoes and patients at the genotype level.Results: We collected a total of 583 adult Ae. aegypti mosquitoes; of which, we individually tested 359 female mosquitoes for the presence of DENV. Ten (2.8%) among the 359 female mosquitoes were positive for the presence of DENV. We detected DENV-1, DENV-2, and DENV-4 in the field-collected mosquitoes, which were consistent with the serotypes concurrently infecting patients. Sequencing and phylogenetic analyses of the detected DENVs based on the partial envelope (E) gene revealed three genotypes concurrently present in the sampled mosquitoes and patients during the study period, namely: DENV-1 genotype IV, DENV-2 Cosmopolitan genotype, and DENV-4 genotype II.Conclusions: In this study, we demonstrate the utility of the one-step multiplex real-time RT-PCR assay in the individual-based DENV surveillance of mosquitoes. Our findings reinforce the significance of detecting and monitoring virus activity in local mosquito populations, which is critical for dengue prevention and control activities.
Interpersonal Counselling for Adolescent Depression delivered by Youth Mental Health Workers without Core Professional Training: A Feasibility Randomised Controlled Trial study protocol
Authors: Abotsie Gabriel , Cestaro Viktoria , Gee Brioney , Murdoch Jamie , Katangwe Thando , Meiser-Stedman Richard Richard , Shepstone Lee , Turner David , Tulk Susie , Jarret Sharon , Wilson Jon , Clarke Timothy , Bonnie Teague , Wilkinson Paul
Published: November 2020

Background: Depression is a common health problem during adolescence and is associated with adverse academic, social and health outcomes. To meet demand for treatment for adolescent depression, there is a need for evidence-based interventions suitable for delivery outside of specialist Child and Adolescent Mental Health Services (CAMHS). Interpersonal Counselling for Adolescents (IPC-A), is a brief manualised intervention for adolescent depression suitable for delivery by staff who are not qualified health professionals following participation in a brief training course. While initial piloting within Local Authority services has generated promising results, the effectiveness and cost-effectiveness of IPC-A has yet to be established. This study aims to assess the feasibility of a randomised controlled trial (RCT), evaluating the effectiveness and cost-effectiveness of IPC-A delivered by staff without core professional training in comparison to current provision. Method: Feasibility RCT with process evaluation using ethnographic methodology. Eligible young people (n=60) will be randomised in a 1:1 ratio to receive either IPC-A or treatment as usual (TAU). Participants will be assessed pre-randomisation (baseline) and followed up at 5, 10 and 23 weeks post-randomisation. A parallel process evaluation will generate understanding of intervention implementation across services and explore the acceptability of the intervention from the perspective of young people and other key stakeholders.Participants: Young people aged 12-18 years presenting to non-specialist services with symptoms of depression. Youth workers, young people and stakeholders will participate in the process evaluation.Discussion: The need for effective and accessible interventions for young people with mild/sub-threshold depression who in most cases, do not meet the threshold for mainstream mental health services is long overdue. The primary output of this feasibility trial will be the design of the subsequent full-scale trial. If the results of the current study indicate that this would be feasible, we intend to progress to a multi-site, assessor-blind, superiority RCT of the effectiveness and cost-effectiveness of IPC-A in comparison to TAU for adolescents presenting to non-specialist services with depressive symptoms. If satisfactory solutions to any problems encountered cannot be identified, alternative research designs will be considered. If proven effective, an IPC-A training programme could be implemented.Trial registry: ISRCTN registry, ISRCTN82180413. Registered 31 December 2019, https://doi.org/10.1186/ISRCTN82180413
Knowledge, socio-cognitive perceptions and the practice of hand hygiene and social distancing during the COVID-19 pandemic: A cross-sectional study of UK university students
Authors: Barrett Christine , Cheung Kei Long
Published: November 2020

BackgroundDuring the first wave of the COVID-19 pandemic, social distancing and hand hygiene have been the primary means of reducing transmission in the absence of effective treatments or vaccines, but understanding of their determinants is limited. This study aimed to investigate knowledge and socio-cognitive perceptions, and their associations with such protective behaviours, in UK university students. MethodsA cross-sectional online survey of 293 students was undertaken on 13 May 2020. Survey questions addressed demographics, knowledge of the disease and effectiveness of the protective measures, risk perception, socio-cognitive perceptions (e.g. attitude, social support, and self-efficacy), habit, time factors and trust, as well as the hand hygiene and social distancing behaviours. Multiple linear regression was used to identify the strongest associations of potential determinants with behaviour.ResultsParticipants reported high levels of social distancing with 88.9 % answering “Mostly” or “Always” for every activity, but only 42.0% reporting the same for all hand hygiene activities. Knowledge of the effectiveness of each activity in preventing transmission was high, with 90.7% and 93.5% respectively identifying at least 7 of 8 hand hygiene or 9 of 10 social distancing activities correctly. Habit (β = 0.39, p =0.001) and time factors (β = 0.28, p =0.001) were the greatest contributors to unique variance in hand hygiene behaviour, followed by ethnicity (β = -0.13, p =0.014) and risk perception (β = 0.13, p = 0.016). For social distancing behaviour, the determinants were self-efficacy (β = 0.25, p <0.001), perceived advantages (β = 0.15, p = 0.022), trust in policy (β = 0.14, p = 0.026) and gender (β = -0.14, p = 0.016). Regression models explained 40% hand hygiene and 25% social distancing variance.ConclusionsThis study indicated that communications about effectiveness of hand hygiene and social distancing behaviours had been effective in terms of knowledge acquisition. However, in the light of likely second waves of COVID-19, attention to maintaining social distancing behaviour and improving hand hygiene behaviour may need to address more difficult areas of changing habits, overcoming time factors and building trust, as well as interventions to increase self-efficacy and address risk perception concerns.
Analysis of serum levels of organochlorine pesticides and related factors in Parkinson’s disease
Authors: Xu Shaoqing , Yang Xiaodong , Qian Yiwei , Wan Dayong , Sun Fenghua , Luo Qian , Song Yanyan , Xiao Qin
Published: November 2020

Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.
Dietary seaweed-derived polysaccharides improve growth performance of weaned pigs through maintaining intestinal barrier function and modulating gut microbial populations
Authors: Zou Tiande , Yang Jin , Guo Xiaobo , He Qin , Wang Zirui , You Jinming
Published: November 2020

Background: Seaweed-derived polysaccharides (SDP) represent an attractive source of prebiotic nutraceuticals for the food and animal husbandry industry. However, the mechanism by which SDP from Enteromorpha mediates pig growth are not fully understood. This study aimed to investigate how SDP supplementation influences the growth performance and intestinal health in weaned pigs.Results: In Exp. 1, 240 weaned pigs were randomly assigned to four dietary treatments and fed with a basal diet or a basal diet containing 200, 400 or 800 mg/kg SDP, respectively, in a 21-d trial. Pigs on the 400 or 800 mg/kg SDP-supplemented group had greater ADG and lower F/G ratio than those on the control group (P＜0.05). In Exp. 2, 20 male weaned pigs were randomly assigned to two treatments and fed with a basal diet (CON group) or a basal diet supplemented with 400 mg/kg SDP (the optimum does from Exp. 1), in a 21-d trial. Pigs fed the SDP diet had greater ADG, the concentrations of serum IL-6 and TNF-α and the activities of glutathione peroxidase, superoxide dismutase and catalase (P＜0.05), and lower F/G, diarrhea rate, as well as serum D-lactate concentrations and diamine oxidase activity (P＜0.05). Moreover, dietary SDP supplementation enhanced secretory immunoglobulin A content, villus height and villous height: crypt depth ratio in small intestine, as well as the lactase and maltase activities in jejunum mucosa (P＜0.05). SDP supplementation elevated the mRNA levels of inflammatory response-related genes (IL-6, TNF-α, TLR4, TLR6 and MyD88), and the mRNA and protein levels of ZO-1, Claudin-1 and Occludin in jejunum mucosa (P＜0.05). Importantly, SDP not only increased the Lactobacillus population but also reduced the Escherichia coli population in cecum (P＜0.05). Furthermore, SDP increased acetic acid and butyric acid concentrations in cecum (P＜0.05).Conclusions: These results not only suggest a beneficial effect of SDP on growth performance and intestinal barrier functions, but also offer potential mechanisms behind SDP-facilitated intestinal health in weaned pigs.
Once is rarely enough: Can social prescribing facilitate adherence to non-clinical community and voluntary sector health services? Empirical evidence from Germany
Authors: Golubinski Veronika , Wild Eva-Maria , Winter Vera , Schreyögg Jonas
Published: November 2020

Background: Non-clinical health interventions provided by the voluntary and community sector can improve patients’ health and well-being and reduce pressure on primary and secondary care, but only if patients adhere to them. This study provides novel insights into the impact of doctor referrals to such services, known as social prescribing, on patients’ adherence to them.Methods: Using a negative binomial model, we analysed electronic visitor records from a community health advice and navigation service in Germany between January 2018 and December 2019 to determine whether social prescribing was associated with greater adherence to the service (measured in terms of return visits) compared to patients who self-referred. We also explored whether this effect differed according to patient characteristics.Results: Based on 1,734 observations, we found that social prescribing was significantly associated with a greater number of return visits compared to patient self-referrals (p<0.05). For patients who visited the service because of psychological concerns, the effect of social prescribing was lower. For all other patient characteristics, the effect remained unchanged, suggesting relevance to all other patient groups.Conclusions: The results of our study indicate that social prescribing may be an effective way to facilitate adherence to non-clinical community and voluntary sector health services. This knowledge is important for policy makers who are deciding whether to implement or expand upon social prescribing schemes. Trial registration: Not applicable
Estimation of the LDL Subclasses in Ischemic Stroke as a Risk Factor in a Chinese population
Authors: Duan Ruisheng , Xue Wenjun , Wang Kunpeng , Yin Nan , Hao Hongyu , Chu Hongshan , Wang Lijun , Meng Peng , Diao Le
Published: November 2020

Background: Acute ischemic stroke (AIS) is one of the leading causes of mortality and long-term disability worldwide. Our study aims to clarify the role of low-density lipoproteins (LDL) subclasses in the occurrence of AIS and develop a risk prediction model based on these characteristics to identify high-risk people.Methods: Five hundred and sixty-six patients with AIS and 197 non-AIS controls were included in this study. Serum lipids and other baseline characteristics including fasting blood glucose (GLU), serum creatinine (Scr), and blood pressure were investigated in relation to occurrence of AIS. The LDL subfractions were classified and measured with the Lipoprint System by a polyacrylamide gel electrophoresis technique.Results: Levels of LDL-3, LDL-4 and LDL-5 subclasses were significantly higher in the AIS group compared to the non-AIS group and lower level of LDL-1 was prevalent in the AIS patients. Consistently, Spearman correlation coefficient demonstrated that sd‐demonevels, especially LDL-3 and LDL-4 levels, were significantly positively correlated with AIS. Furthermore, there is a significant positive correlation between small dense LDL (sd-LDL, that is LDL-3 to 7) levels and serum lipids including total cholesterol (TC), Low density lipoprotein cholesterol (LDL‐C), and Triglyceride (TG). Increased LDL-3 and LDL-4 as well as decreased LDL-1 and LDL-2 were correlated to the occurrence of AIS, even in the people with normal LDL-C levels. A new prediction model including 12 variables can accurately predict the AIS risk in Chinese patients (AUC=0.82±0.04).Conclusions: Levels of LDL subclasses should be considered in addition to serum LDL-C in assessment and management of AIS. A new prediction model based on clinical variables including LDL subtractions can help clinicians identify high of AIS, even in the people with norm.
Assessment of D-dimer for ruling out peripherally inserted central catheter-associated upper extremity venous thrombosis: a diagnostic accuracy study
Authors: Liu Wanli , He Lianxiang , Zeng Wenjing , Yue Liqing , Wei Jie , Zeng Shuangshuang , Wang Xiang , Gong Zhicheng
Published: November 2020

Background: With the extensive use of peripherally inserted central catheter (PICC), PICC-associated venous thrombosis (VT) has become one of the most important complications in the hospital. To reduce unnecessary Color Doppler Ultrasound (CDU) or imaging tests, D-dimer values are usually used to exclude VT for patients with low VT risk. There is little evidence for the usefulness of the D-dimer level as an independent diagnostic marker for excluding PICC-associated VT.Aims: To examine the effectiveness of D-dimer values to be used as an independent diagnostic marker for excluding PICC-associated Upper Extremity Venous Thrombosis(UEVT).Methods:Records were reviewed for 281 patients who underwent PICC insertion over the two years period in Xiangya Hospital Central South University.The patients were categorized into the UEVT unlikely group (<2 points) and the UEVT likely group (≥2 points) according to the Constans Clinical Decision Score( Constans score) post PICC insertion, before extubation. After the score was determined, the patients underwent a D-dimer test and CDU within 7 days after D-dimer test.Results: Among 281 patients, 180 patients (36%, 95%CI:30.6%-41.8%) had negative D-dimer results, 39 of 180 patients had VT despite having a negative D-dimer result, resulting in a failure rate of 21.7% (95% CI: 16.3–28.3%).The NPV of PICC-associated VT in the cancer group (80.0%,95% CI: 73.2–85.4%) was higher than that of the non-cancer group (60.0%,95% CI: 35.7–80.2%). The NPV of PICC-associated DVT(Deep Venous Thrombosis) (84.9%,95% CI: 78.7–89.6%) was lower than that of the PICC-associated SVT(Superficial Venous Thrombosis) (91.0% ,95% CI: 85.4–94.6%).Conclusion: The D-dimer levels maybe should not be used as a diagnostic index to rule out PICC-associated VT to avoid missed diagnosis of PICC-related VT, which may cause adverse consequences.
Removal of fermentation inhibitors from pre-hydrolysis liquor using polystyrene divinylbenzene resin
Authors: Huang Caoxing , Zheng Yayue , Lin Wenqian , Shi Yuxuan , Huang Guohong , Yong Qiang
Published: November 2020

Background: The presence of soluble lignin, furfural and hydroxymethylfurfural (HMF) in industrial pre-hydrolysis liquor (PHL) from the pulping process can inhibit its bioconversion into bioethanol and other biochemicals. Although various technologies have been developed to remove these inhibitors, certain amounts of sugars are also inevitably removed during the treatment process. Hence, polystyrene divinylbenzene (PS-DVB) resin was used as an adsorptive material to simultaneously remove fermentation inhibitors while retaining sugars with high yields to improve the fermentability of PHL after acid-hydrolysis by enriching its xylose concentration. The fermentability of acid-hydrolyzed PHL (A-PHL) was evaluated by the bioconversion into ethanol and xylosic acid (XA) after treatment with PS-DVB resin.Results: The results showed that the highest xylose concentration (101.1 g/L) in PHL could be obtained by acid-hydrolysis at 100 oC for 80 min with 4% acid, while the concentration of fermentation inhibitors (furfural, HMF and lignin) in PHL could also be significantly improved during the acid-hydrolysis process. After treatment with PS-DVB resin, not only were 97% of lignin, 92% of furfural, and 97% of HMF removed from A-PHL, but also 96% of xylose was retained for subsequent fermentation. With resin treatment, the fermentability of A-PHL could be improved by 162-282% for ethanol production from A-PHL containing 30-50 g/L xylose and by 18-828% for XA production from A-PHL containing 90-150 g/L xylose. Conclusions: These results confirmed that PS-DVB resin can remove inhibitors from PHL before producing value-added products by bioconversion. In addition, this work will ideally provide a concept for producing value-added chemicals from pre-hydrolysis liquor, which is regarded as the waste stream in the pulping process.
Beneficial effect of indigo naturalis on acute lung injury induced by influenza A virus
Authors: Tu Peng , Tian Rong , Lu Yan , Zhang Yunyi , Zhu Haiyan , Ling Lijun , Li Hong , Chen Daofeng
Published: November 2020

Background: Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of indigo naturalis on ALI induced by influenza A virus (IAV) in mice.Method: The anti-influenza and anti-inflammatory properties of aqueous extract of indigo naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg·kg-1/d) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA.Result: INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05).Conclusion: The results showed that INae alleviated IAV induced ALI in mice. The effect of INAE might be related with its anti-influenza, anti-inflammatory and anti-oxidation properties, which give a hint that indigo naturalis might be effective on respiratory viruses infected acute lung injury or SAR-CoV-2 caused COVID-19.