bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-discrete-elements concrete shear deformation model: Formulation and application in the seismic evaluation of reinforced concrete shear walls
Authors: Oudah Fadi , El-Hacha Raafat
Published: July 2020

Shear deformation in reinforced concrete structures is of a complex nature. A thorough understanding of the interaction between the shear strength, flexural strength, and flexural ductility is not yet achieved. A new shear-deformation-based theory is proposed and validated in this study. The so-called two-discrete-elements (TDE) shear deformation theory idealizes reinforced concrete members as series of two discrete types of elements: S-elements and C-elements. The S-elements are used to model the regions of concrete reinforced to resist flexural and shear deformation using longitudinal and transverse steel reinforcement, while the C-elements are used to model the reinforced concrete sections bounded by the stirrups. The compatibility between the two types of elements is enforced by controlling the crack angle. The formulation of the newly developed theory is discussed in terms of equilibrium of forces, compatibility within the elements, compatibility at the interface, and constitutive material modeling. The theory was applied to evaluate the deformability of reinforced concrete shear walls subjected to lateral loads for seismic design applications. It was also implemented to generate sample design charts referred to as axial–moment–shear interaction diagrams. These diagrams can be used to design shear walls subjected to combined action of axial load, moment, and shear as opposed to the conventional interaction diagrams in which only the axial load versus moment relationship is considered. Analysis results indicated the adequacy of the proposed theory in capturing the shear strength degradation and predicting structural failures controlled by the shear capacity.
Banded amphibolites in the Alps: a new interpretation in relation to early Paleozoic peraluminous magmatism
Authors: Zurbriggen Roger
Published: July 2020

The Strona-Ceneri Zone is located south of the Insubric line, where Alpine overprint is mainly brittle and of low grade or even absent. Apart from the unmetamorphic Permo-Carboniferous sediments and intrusiva the Strona-Ceneri Zone is an Ordovician gneiss complex composed of paragneisses, migmatites, peraluminous orthogneisses and banded amphibolites associated with meta-gabbros and meta-ultramafics. Despite of the individual characters of the other Ordovician gneiss terranes north of the Insubric line, most prominently the Aar Massif, the Gotthard, Silvretta and Ötztal nappes, they show analogous lithological formations and pre-Mesozoic structures indicating similar genetic processes. A revision of geological maps and new field observations in these gneiss terranes indicate characteristic spatial relationships of banded amphibolite formations with migmatites and orthogneisses. The contrasting chemistries of the peraluminous rocks (para- and orthogneisses) and the basaltic amphibolites with a lack of intermediate lithologies in between can be explained by the setting of peraluminous arc magmatism within a subduction–accretion complex. In this model the amphibolites represent primary basalts which ponded at the base of the subduction–accretion complex and delivered the heat for the production of peraluminous melts. Volume estimations indicate a “zone of intermingling” composed of immiscible basalts and peraluminous melts with a total thickness of several kilometers. In this “zone of intermingling” the protoliths of the banded amphibolite formations were generated. Steep strike-slip faults, which are important structures for the syn-magmatic cratonization of subduction–accretion complexes, provide pathways for the emplacement of magmas, migmatites and intermingled materials. This results in the formation of steeply oriented sheets of orthogneisses, deformed migmatites and banded amphibolite formations, respectively. Finally, the paper lists many other peri-Gondwanan regions with an early Paleozoic peraluminous arc magmatism, indicating a similar setting on a global scale.
Meridian study on the response current affected by electrical pulse and acupuncture
Authors: Hung Yu-Chiang , Chen Wen-Chung , Chang Ting-Chang , Zheng Hao-Xuan , Liu Yan-Wen , Tan Yung-Fang , Lin Shih-Kai , Lu Ying-Hsin , Hu Wen-Long , Tsai Tsung-Ming
Published: July 2020

Acupuncture and its meridians are important components of traditional Chinese medicine, and numerous opinions have been previously expressed regarding these meridians. This study aims to explore the phenomenon of meridians from the perspective of electronic physics by studying these meridians for the response current affected by electrical pulse and acupuncture. In this study, acupuncture which applies an electrical pulse was used to research the physical properties of the meridians. Different kinds of pulses were applied to the human body to realize abnormal electrical signals. Comparing these electrical measurement results with the isothermal transient ionic current (ITIC) theory, we found that the transmission of meridian messages may be related to ion conduction. The movement of ions induced by acupuncture and electrical stimulation can lead to drift and diffusion currents through the meridians. The ionic conduction of meridian hypothesis is proved in that the substances delivered by meridians are in fact ions.
A database for ITS2 sequences from nematodes
Authors: Workentine Matthew L. , Chen Rebecca , Zhu Shawna , Gavriliuc Stefan , Shaw Nicolette , Rijke Jill de , Redman Elizabeth M. , Avramenko Russell W. , Wit Janneke , Poissant Jocelyn , Gilleard John S.
Published: July 2020

Background

Marker gene surveys have a wide variety of applications in species identification, population genetics, and molecular epidemiology. As these methods expand to new types of organisms and additional markers beyond 16S and 18S rRNA genes, comprehensive databases are a critical requirement for proper analysis of these data.

Results

Here we present an ITS2 rDNA database for marker gene surveys of both free-living and parasitic nematode populations and the software used to build the database. This is currently the most complete and up-to-date ITS2 database for nematodes and is able to reproduce previous analysis that used a smaller database.

Conclusions

This database is an important resource for researchers working on nematodes and also provides a tool to create ITS2 databases for any given taxonomy.
Growth performance and element concentrations reveal the calcicole-calcifuge behavior of three Adiantum species
Authors: Liao Jian Xiong , Liang Dan Yang , Jiang Qian Wen , Mo Ling , Pu Gao Zhong , Zhang Deng
Published: July 2020

Background

The calcicole or calcifuge behavior of wild plants has been related to element deficiency or toxicity. For fern species, however, knowledge about their adaptive differences and responses to soil environmental changes is virtually absent. In the karst regions of southern China, mostAdiantumspecies favor calcareous soils, butA. flabellulatumprefers acidic soils. Such contrasting preferences for soil types in the same genus are interesting and risky because their preferred soils may “pollute” each other due to extreme precipitation events. We mixed calcareous and acidic soils at 1:1 (v/v) to simulate the “polluted” soils and grew threeAdiantumspecies (the calcicoleA. capillus-venerisf.dissectumandA. malesianumand the calcifugeA. flabellulatum) on the calcareous, acidic and mixed soils for 120 d and assessed their growth performance and element concentrations.

Results

The calcareous soil showed the highest pH, Ca, Mg and P concentrations but the lowest K concentration, followed by the mixed soil, and the acidic soil. After 120 d of growth, the calcifugeA. flabellulatumon the calcareous and mixed soils exhibited lower SPAD and relative growth rate (RGR) than those on the acidic soil, and its leaf and root Ca, Mg and Fe concentrations were higher and K was lower on the calcareous soil than on the acidic soil. The calcicoleA. capillus-venerisf.dissectumon the calcareous soil had similar leaf element concentrations and RGR with those on the mixed soil, but their leaf Ca, Fe and Al were lower and leaf P and K concentrations, SPAD and RGR were higher than those on the acidic soil. For the calcicoleA. malesianum, leaf Ca, Fe and Al were lowest and leaf P and RGR were highest when grown on the mixed soil, intermediated on the calcareous soil, and on the acidic soil. Compared withA. malesianum,A. capillus-venerisf.dissectumhad lower leaf Ca, Fe and Al but higher leaf Mg concentration when grown on the same calcareous or mixed soils.

Conclusions

A. capillus-venerisf.dissectumis a low leaf Ca calcicole species whileA. malesianumis an Al accumulating calcicole species. They can effectively take up P and K to leaves and hence can thrive on calcareous soils. In contrast, the calcifugeA. flabellulatumgrown on calcareous soils is stunted. Such growth performance may be attributed to the increased leaf Ca and decreased leaf K concentration. If their preferred soils are “polluted”,A. flabellulatumcan grow worse,A. capillus-venerisf.dissectumcan remain almost unaffected whileA. malesianumwill perform better.
Study protocol for a hospital-to-home transitional care intervention for older adults with multiple chronic conditions and depressive symptoms: a pragmatic effectiveness-implementation trial
Authors: Markle-Reid Maureen , McAiney Carrie , Ganann Rebecca , Fisher Kathryn , Gafni Amiram , Gauthier Alain P. , Heald-Taylor Gail , McElhaney Janet , Ploeg Jenny , Urajnik Diana J. , Valaitis Ruta , Whitmore Carly
Published: July 2020

Background

Older adults (> 65 years) with multiple chronic conditions (MCC) and depressive symptoms experience frequent transitions between hospital and home. Care transitions for this population are often poorly coordinated and fragmented, resulting in increased readmission rates, adverse medical events, decreased patient satisfaction and safety, and increased caregiver burden. There is a dearth of evidence on best practices in the provision of transitional care for older adults with MCC and depressive symptoms transitioning from hospital-to-home. This paper presents a protocol for a two-armed, multi-site pragmatic effectiveness-implementation trial of Community Assets Supporting Transitions (CAST), an evidence-informed nurse-led six-month intervention that supports older adults with MCC and depressive symptoms transitioning from hospital-to-home. The Collaborative Intervention Planning Framework is being used to engage patients and other key stakeholders in the implementation and evaluation of the intervention and planning for intervention scale-up to other communities.

Methods

Participants will be considered eligible if they are > 65 years, planned for discharged from hospital to the community in three Ontario locations, self-report at least two chronic conditions, and screen positive for depressive symptoms. A total of 216 eligible and consenting participants will be randomly assigned to the control (usual care) or intervention (CAST) arm. The intervention consists of tailored care delivery comprising in-home visits, telephone follow-up and system navigation support. The primary measure of effectiveness is mental health functioning of the older adult participant. Secondary outcomes include changes in physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health and social service use and cost, from baseline to 6- and 12-months. Caregivers will be assessed for caregiver strain, depressive symptoms, anxiety, health-related quality of life, and health and social service use and costs. Descriptive and qualitative data from older adult and caregiver participants, and the nurse interventionists will be used to examine implementation of the intervention, how the intervention is adapted within each study region, and its potential for sustainability and scalability to other jurisdictions.

Discussion

A nurse-led transitional care strategy may provide a feasible and effective means for improving health outcomes and patient/caregiver experience and reduce service use and costs in this vulnerable population.

Trial registration

# NCT03157999.

Registration Date: April 4, 2017.
Finding gaps in TB notifications: spatial analysis of geographical patterns of TB notifications, associations with TB program efforts and social determinants of TB risk in Bangladesh, Nepal and Pakistan
Authors: van Gurp Margo , Rood Ente , Fatima Razia , Joshi Pushpraj , Verma Sharat Chandra , Khan Ahmadul Hasan , Blok Lucie , Mergenthaler Christina , Bakker Mirjam Irene
Published: July 2020

Background

In order to effectively combat Tuberculosis, resources to diagnose and treat TB should be allocated effectively to the areas and population that need them. Although a wealth of subnational data on TB is routinely collected to support local planning, it is often underutilized. Therefore, this study uses spatial analytical techniques and profiling to understand and identify factors underlying spatial variation in TB case notification rates (CNR) in Bangladesh, Nepal and Pakistan for better TB program planning.

Methods

Spatial analytical techniques and profiling was used to identify subnational patterns of TB CNRs at the district level in Bangladesh (N = 64, 2015), Nepal (N = 75, 2014) and Pakistan (N = 142, 2015). A multivariable linear regression analysis was performed to assess the association between subnational CNR and demographic and health indicators associated with TB burden and indicators of TB programme efforts. To correct for spatial dependencies of the observations, the residuals of the multivariable models were tested for unexplained spatial autocorrelation. Spatial autocorrelation among the residuals was adjusted for by fitting a simultaneous autoregressive model (SAR).

Results

Spatial clustering of TB CNRs was observed in all three countries. In Bangladesh, TB CNR were found significantly associated with testing rate (0.06%,p < 0.001), test positivity rate (14.44%,p < 0.001), proportion of bacteriologically confirmed cases (− 1.33%,p < 0.001) and population density (4.5*10–3%,p < 0.01). In Nepal, TB CNR were associated with population sex ratio (1.54%,p < 0.01), facility density (− 0.19%,p < 0.05) and treatment success rate (− 3.68%,p < 0.001). Finally, TB CNR in Pakistan were found significantly associated with testing rate (0.08%,p < 0.001), positivity rate (4.29,p < 0.001), proportion of bacteriologically confirmed cases (− 1.45,p < 0.001), vaccination coverage (1.17%,p < 0.001) and facility density (20.41%,p < 0.001).

Conclusion

Subnational TB CNRs are more likely reflective of TB programme efforts and access to healthcare than TB burden. TB CNRs are better used for monitoring and evaluation of TB control efforts than the TB epidemic. Using spatial analytical techniques and profiling can help identify areas where TB is underreported. Applying these techniques routinely in the surveillance facilitates the use of TB CNRs in program planning.
Testing the regulatory framework in South Africa – a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis
Authors: Happel Anna-Ursula , Singh Ravesh , Mitchev Nireshni , Mlisana Koleka , Jaspan Heather B. , Barnabas Shaun L. , Passmore Jo-Ann S.
Published: July 2020

Background

Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.

Methods

Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7–10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.

Results

The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24–1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.

Conclusion

Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.

Trial registration

This trial was registered on 17 October 2017 with the South African National Clinical Trial Register (http://www.sanctr.gov.za/; BV-trial1;DOH-27-1117-5579).
Preeclampsia in pregnancy affecting the stemness and differentiation potency of haematopoietic stem cell of the umbilical cord blood
Authors: Nordin Fazlina , Idris Mohd Razif Mohd , Mahdy Zaleha Abdullah , Wahid S. Fadilah Abd
Published: July 2020

Background

Umbilical cord blood (UCB) has been proposed as the potential source of haematopoietic stem cells (HSC) for allogeneic transplantation. However, few studies have shown that a common disease in pregnancy such as preeclampsia would affect the quality of UCB-HSC. Total nucleated cell count (TNC) is an important parameter that can be used to predict engraftment including UCB banking. Colony forming unit (CFU) assay is widely used as an indicator to predict the success of engraftment, since direct quantitative assay for HSC proliferation is unavailable. The aim of this study is to investigate the effects of preeclampsia in pregnancy on the stemness and differentiation potency of UCB-HSC.

Methods

Mononuclear cells (MNC) were isolated from UCB and further enriched for CD34+ cells using immune-magnetic method followed by CFU assay. A panel of HSC markers including differentiated haematopoietic markers were used to confirm the differentiation ability of UCB-HSC by flow cytometry analysis.

Results/ discussion

The HSC progenitor’s colonies from the preeclampsia group were significantly lower compared to the control. This correlates with the low UCB volume, TNC and CD34+ cells count. In addition, the UCB-enriched CD34+ population were lymphoid progenitors and capable to differentiate into natural killer cells and T-lymphocytes.

Conclusion

These findings should be taken into consideration when selecting UCB from preeclamptic mothers for banking and predicting successful treatment related to UCB transplant.
Introducing the trajectory Touchpoint technique: a systematic methodology for capturing the service experiences of palliative care patients and their families
Authors: Sudbury-Riley Lynn , Hunter-Jones Philippa , Al-Abdin Ahmed
Published: July 2020

Background

Evaluation of palliative care services is crucial in order to ensure high quality care and to plan future services in light of growing demand. There is also an acknowledgement of the need to better understand patient experiences as part of the paradigm shift from paternalistic professional and passive patient to a more collaborative partnership. However, while clinical decision-making is well-developed, the science of the delivery of care is relatively novel for most clinicians. We therefore introduce the Trajectory Touchpoint Technique (TTT), a systematic methodology designed using service delivery models and theories, for capturing the voices of palliative care service users.

Methods

We used design science research as our overarching methodology to build our Trajectory Touchpoint Technique. We also incorporated a range of kernel theories and service design models from the wider social sciences. We developed and tested our Trajectory Touchpoint Technique with palliative care patients and their families (n = 239) in collaboration with different hospices and hospital-based palliative care providers (n = 8).

Results

The Trajectory Touchpoint Technique is user-friendly, enables systematic data collection and analysis, and incorporates all tangible and intangible dimensions of palliative care important to the service user. These dimensions often go beyond clinical care to encompass wider aspects that are important to the people who use the service. Our collaborating organisations have already begun to make changes to their service delivery based on our results.

Conclusions

The Trajectory Touchpoint Technique overcomes several limitations of other palliative care evaluation methods, while being more comprehensive. The new technique incorporates physical, psychosocial, and spiritual aspects of palliative care, and is user-friendly for inpatients, outpatients, families, and the bereaved. The new technique has been tested with people who have a range of illnesses, in a variety of locations, among people with learning disabilities and low levels of literacy, and with children as well as adults. The Trajectory Touchpoint Technique has already uncovered many previously unrecognised opportunities for service improvement, demonstrating its ability to shape palliative care services to better meet the needs of patients and their families.
The impact of healthcare worker influenza vaccination on nosocomial influenza in a tertiary hospital: an ecological study
Authors: Wei Wycliffe Enli , Fook-Chong Stephanie , Chen Wen Kai , Chlebicki Maciej Piotr , Gan Wee Hoe
Published: July 2020

Background

To protect hospitalized patients, who are more susceptible to complications of influenza, seasonal influenza vaccination of healthcare workers (HCW) has been recommended internationally. However, its effectiveness is still being debated. To assess the effectiveness of HCW influenza vaccination, we performed an ecological study to evaluate the association between healthcare worker influenza vaccination and the incidence of nosocomial influenza in a tertiary hospital within Singapore between 2013 and 2018.

Methods

Nosocomial influenza was defined as influenza among inpatients diagnosed 7 days or more after admission by laboratory testing, while healthcare worker influenza vaccination rate was defined as the proportion of healthcare workers that was vaccinated at the end of each annual seasonal vaccination exercise. A modified Poisson regression was performed to assess the association between the HCW vaccination rates and monthly nosocomial influenza incidence rates.

Results

Nosocomial influenza incidence rates followed the trend of non-nosocomial influenza, showing a predominant mid-year peak. Across 2,480,010 patient-days, there were 256 nosocomial influenza cases (1.03 per 10,000 patient-days). Controlling for background influenza activity and the number of influenza tests performed, no statistically significant association was observed between vaccination coverage and nosocomial influenza incidence rate although a protective effect was suggested (IRR 0.89, 95%CI:0.69–1.15,p = 0.37).

Conclusion

No significant association was observed between influenza vaccination rates and nosocomial influenza incidence rates, although a protective effect was suggested. Aligning local HCW vaccine timing and formulation to that of the Southern Hemisphere may improve effectiveness. HCW vaccination remains important but demonstrating its effectiveness in preventing nosocomial influenza is challenging.
Comparison of individual and neighbourhood socioeconomic status in case mix adjustment of hospital performance in primary total hip replacement in Sweden: a register-based study
Authors: Mesterton Johan , Willers Carl , Dahlström Tobias , Rolfson Ola
Published: July 2020

Background

Case mix adjustment is a pre-requisite for valid measurement of healthcare performance and socioeconomic status (SES) is important to account for. Lack of information on individual-level SES has led to investigations into using a proxy for SES based on patient area of residence. The objective of this study was to use neighbourhood SES for case mix adjustment of performance indicators in total hip replacement (THR) in Sweden, and to compare with use of individual SES.

Methods

Data from patient administrative systems and the Swedish Hip Arthroplasty Register were extracted for all patients undergoing THR in four Swedish regions. For each subject, individual data and neighbourhood data on country of birth, educational level, and income were provided by Statistics Sweden. Three variables were selected for analysis of performance; EQ-5D, hip pain and length of stay (LoS). In addition to socioeconomic information, several important clinical characteristics were used as case mix factors. Regression analysis was used to study each variable’s impact on the three outcome variables and model fit was evaluated using mean squared error.

Results

A total of 27,121 patients operated between 2010 and 2016 were included in the study. Both educational level and income were higher when based on neighbourhood information than individual information, while proportion born in Sweden was similar. Higher SES was generally found to be associated with better outcomes and lower LoS, albeit with certain differences between the different measures of SES. The predictive ability of the models was increased when adding information on SES to the clinical characteristics. The increase in predictive ability was higher for individual SES compared to neighbourhood SES. When analysing performance for the two providers with most diverging case mix in terms of SES, the inclusion of SES altered the relative performance using individual as well as neighbourhood SES.

Conclusions

Incorporating SES improves case mix adjustment marginally compared to using only clinical information. In this patient group, geographically derived SES was found to improve case mix adjustment compared to only clinical information but not to the same extent as actual individual-level SES.
USP4 function and multifaceted roles in cancer: a possible and potential therapeutic target
Authors: Wang Yizhi , Zhou Li , Lu Jun , Jiang Bolun , Liu Chengxi , Guo Junchao
Published: July 2020

Cancer remains one of the major culprits causing disease-related deaths and leads to a high morbidity and similar mortality. Insidious onset, difficult early detection and a lack of broad-spectrum and effective multi-cancer therapeutic targets have limited the prolongation of cancer patients’ survival for decades. Therefore, a versatile therapeutic target which is involved in various cancer-related signaling pathways and different cancers may be more effective for cancer targeted therapy. USP4, one of the DUBs members which participates in deubiquitination, an inverse process of ubiquitination, can regulate various classical cancer-related signaling pathways, and thereby plays a vital role in some pathological and physiological processes including tumor initiation and progression. Recently, USP4 has been found to exert versatile influences on cells proliferation, migration and invasion, also apoptosis of various tumors. Moreover, USP4 can also act as a prognostic biomarker in several cancers. This review will give a comprehensive introduction of USP4 about its regulatory mechanisms, related signaling pathways, pathophysiological functions and the roles in various cancers which may help us better understand its biological functions and improve future studies to construct suitable USP4-targeted cancer therapy system.
Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Chewaka District, Ethiopia
Authors: Abamecha Abdulhakim , Yilma Daniel , Addisu Wondimagegn , El-Abid Hassan , Ibenthal Achim , Noedl Harald , Yewhalaw Delenasaw , Moumni Mohieddine , Abdissa Alemseged
Published: July 2020

Background

The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia.

Methods

The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum. A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection.

Results

Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1–98.5) and 96% (95% CI 88.8–99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8–99.2). Based on Kaplan–Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3–11.4). Only three participants 3.8% (95% CI 0.8–10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL.

Conclusions

The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.
Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
Authors: Cheng Jun-Ting , Wang Ying-Ying , Zhu Lin-Zhong , Zhang Ying , Cai Wen-Qi , Han Zi-Wen , Zhou Yang , Wang Xian-Wang , Peng Xiao-Chun , Xiang Ying , Yang Hui-Yu , Cui Shu-Zhong , Ma Zhaowu , Liu Bing-Rong , Xin Hong-Wu
Published: July 2020

Background

Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported.

Methods

Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy.

Results

Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection.

Conclusions

Our findings have important implication to HSV biology, infection, immunity and oHSVs.
MiR-708 inhibits MC3T3-E1 cells against H2O2-induced apoptosis through targeting PTEN
Authors: Zhang Wei , Cui Sheng-Yu , Yi Hong , Zhu Xin-Hui , Liu Wei , Xu You-Jia
Published: July 2020

Background

The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of postmenopausal osteoporosis (PO). MicroRNAs play an important role in regulating apoptosis of MC3T3-E1 cells. However, the role and potential mechanism of miR-708 for regulating H2O2-induced apoptosis is unknown. This study aimed to investigate the protective function of miR-708 in H2O2-induced apoptosis of MC3T3-E1 osteoblasts.

Methods

MC3T3-E1 was co-cultured with H2O2for 8 h, then, flow cytometry, malondialdehyde (MDA), and glutathione peroxidase (Gpx) levels were measured to establish the oxidative model. MiRNA microarray was performed to assess differentially expressed miRNAs between control and H2O2-treated MC3T3-E1 cells. We then performed RT-PCR to identify the relative expression of miR-708 and PTEN. After transfected MC3T3-E1 with miR-708 mimics, flow cytometry, MDA, and Gpx level were performed to identify the apoptosis rate and oxidative stress in these groups. Furthermore, we small interfering RNA of PTEN to identify the role of PTEN in H2O2-induced apoptosis of MC3T3-E1 cells.

Results

H2O2(100 nM) could significantly induce the apoptosis of MC3T3-E1 cells. Moreover, H2O2could significantly increase the MDA level and downregulated Gpx level. RT-PCR found that H2O2significantly decrease the level of miR-708. Compared with H2O2group, H2O2+ miR-708 mimic significantly decreased the apoptosis rate.

Conclusions

miR-708 plays a protective role in H2O2-induced MC3T3-E1 osteoblasts apoptosis and its protective effect is proceeded by regulating ROS level and PTEN expression level.
Correction to: The impact of long dry periods on the aboveground biomass in a tropical forest: 20 years of monitoring
Authors: de Meira Junior Milton Serpa , Pinto José Roberto Rodrigues , Ramos Natália Oliveira , Miguel Eder Pereira , de Oliveira Gaspar Ricardo , Phillips Oliver L.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Stakeholder perspectives of Community Mental Health Forums: a qualitative study in Sierra Leone
Authors: Adams Ben , Vallières Frédérique , Duncan Joshua Abioseh , Higgins Agnes , Eaton Julian
Published: July 2020

Background

Mental health is the leading cause of disability worldwide. In the wake of both a civil war and an Ebola outbreak, Sierra Leone ranks as one of the lowest ranked countries on the Human Development Index (UNDP. Human Development Report 2015, Work for Human Development. The United Nations Development Programme; 2015). The WHO identified Sierra Leone among its priority countries for the piloting of its Mental Health Gap Action Programme (mhGAP). Aligned to these efforts, CBM and their affiliated partners employed the use of Community Mental Health Forums (CMHFs), facilitated by Mental Health Nurses (MHNs), as a sensitive and practical way of engaging key community stakeholders to discuss and address issues of mental health. This study sought firstly, to identify factors that affect the successful implementation of CMHFs, as identified by programme participants. Second, the study sought to identify what changes participants perceived as having taken place as a result of their participation in CMHFs.

Methods

10 MHNs and 52 forum participants were purposely selected to take part in key informant interviews and focus group discussions, conducted across eight districts in Sierra Leone. Interview transcripts were analysed across four rounds of coding, using a mixture of deductive and inductive approaches.

Results

Results identified three themes, Traditional Beliefs and Culture; Health System; and Inclusive Approaches as affecting the implementation of CMHFs in their districts. Participants further perceived that their participation in the Community Mental Health Forums resulted in changes taking place across the themes of Awareness and beliefs, Behaviours towards people experiencing psychological distress, and as leading to greater Collaboration and cooperation between formal and informal mental health practitioners.

Conclusions

Results are discussed in the context of the extant literature and a novel framework, that incorporates multiple best practice recommendations and factors which influence the successful implementation of CMHFs is put forward.
Using metagenomic analysis to assess the effectiveness of oral health promotion interventions in reducing risk for pneumonia among patients with stroke in acute phase: study protocol for a randomized controlled trial
Authors: Wu Juncang , Dai Yuanchang , Lo Edward C. M. , Qi Yinliang , Zhang Ya , Li Quan-li , Dai Ruoxi
Published: July 2020

Background

The prevalence of pneumonia complicating stroke in acute phase has a poor prognosis and higher risk for death. Oral opportunistic pathogens have been reported to be associated with pneumonia among people with compromised health. Oral health promotion is effective in reducing dental plaque among patients with stroke, which is considered as reservoirs for oral opportunistic pathogens. This study evaluates the effectiveness of oral health promotions in reducing the prevalence of pneumonia via its effects on composition and relative abundance of oral opportunistic pathogens.

Methods/design

This study is a randomized, single-blind, parallel trial of 6 months duration. The study is being conducted at one of the largest medical teaching hospitals in Hefei, China. A total of 166 patients with stroke and free from any post-stroke complication will be recruited. After enrollment, patients will be randomized to one of the following groups: (1) oral hygiene instruction (OHI) or (2) OHI, 6-month use of powered tooth brushing, and 0.2% chlorhexidine gluconate mouth rinse (10 ml twice daily). The primary outcome is the prevalence of pneumonia complicating stroke. Patients will be monitored closely for any occurrence of pneumonia over the entire period of this trial. Oral rinse samples will be collected at baseline and multiple follow-up reviews (3, 5, 7 days, and 1, 3, 6 months after baseline). Next-generation sequencing will be employed to detect composition and relative abundances of the microorganism in the oral rinse samples. Questionnaire interviews and clinical oral examinations will be conducted at baseline and 1, 3, and 6 months after baseline.

Discussion

The findings of this trial will provide evidence whether oral health promotion intervention is effective in reducing the prevalence of pneumonia complicating stroke via its effect on the oral microbiome. The analysis of the outcomes of this trial is empowered by metagenomic analysis at 16S rRNA level, which is more sensitive and comprehensive to help us detect how oral health promotion inventions affect the oral microbiome in terms of its composition, relative abundance, and interactions between species, which all may contribute to the occurrence of pneumonia complicating stroke.

Trial registration

ClinicalTrials.govNCT04095780. Registered on 19 September 2019
Enhanced pyruvate metabolism in plastids by overexpression of putative plastidial pyruvate transporter in Phaeodactylum tricornutum
Authors: Seo Seungbeom , Kim Joon , Lee Jun-Woo , Nam Onyou , Chang Kwang Suk , Jin EonSeon
Published: July 2020

Background

The development of microalgal strains for enhanced biomass and biofuel production has received increased attention. Moreover, strain development via metabolic engineering for commercial production is being considered as the most efficient strategy. Pyruvate is an essential metabolite in the cells and plays an essential role in amino acid biosynthesis and de novo fatty acid biosynthesis in plastids. Although pyruvate can be a valuable target for metabolic engineering, its transporters have rarely been studied in microalgae. In this study, we aimed to identify the plastidial pyruvate transporter of Phaeodactylum tricornutum and utilize it for strain development.

Results

We identified putative pyruvate transporter localized in the plastid membrane of Phaeodactylum tricornutum. Transformants overexpressing the pyruvate transporter were generated to increase the influx of pyruvate into plastids. Overexpression of a plastidial pyruvate transporter in P. tricornutum resulted in enhanced biomass (13.6% to 21.9%), lipid contents (11% to 30%), and growth (3.3% to 8.0%) compared to those of wild type during one-stage cultivation.

Conclusion

To regulate the pyruvate influx and its metabolism in plastids, we generated transformants overexpressing the putative plastidial pyruvate transporter in P. tricornutum. They showed that its overexpression for compartmentalizing pyruvate in plastids could be an attractive strategy for the effective production of biomass and lipids with better growth, via enhanced pyruvate metabolism in plastids.
Activity of fungal β-glucosidases on cellulose
Authors: Keller Malene B. , Sørensen Trine H. , Krogh Kristian B. R. M. , Wogulis Mark , Borch Kim , Westh Peter
Published: July 2020

Background

Fungal beta-glucosidases (BGs) from glucoside hydrolase family 3 (GH3) are industrially important enzymes, which convert cellooligosaccharides into glucose; the end product of the cellulolytic process. They are highly active against the β-1,4 glycosidic bond in soluble substrates but typically reported to be inactive against insoluble cellulose.

Results

We studied the activity of four fungal GH3 BGs on cellulose and found significant activity. At low temperatures (10 ℃), we derived the approximate kinetic parameters kcat = 0.3 ± 0.1 s−1 and KM = 80 ± 30 g/l for a BG from Aspergillus fumigatus (AfBG) acting on Avicel. Interestingly, this maximal turnover is higher than reported values for typical cellobiohydrolases (CBH) at this temperature and comparable to those of endoglucanases (EG). The specificity constant of AfGB on Avicel was only moderately lowered compared to values for EGs and CBHs.

Conclusions

Overall these observations suggest a significant promiscuous side activity of the investigated GH3 BGs on insoluble cellulose. This challenges the traditional definition of a BG and supports suggestions that functional classes of cellulolytic enzymes may represent a continuum of overlapping modes of action.
Giant chronic calcified subdural empyema: a case report
Authors: Nour Amal Saleh , Shumbash Kibruyisfaw Zewdie
Published: July 2020

Background

Chronic calcified subdural empyema is an exceedingly rare central nervous system infection with a handful of cases published to date. Reported cases presented with nonspecific clinical signs and symptoms. The duration between the initial onset of symptoms and diagnosis can vary drastically from a few years to up to 46 years. Although there are known predisposing causes, the initial source of infection can sometimes be difficult to identify.

Case presentation

Our patient was a 39-year-old Ethiopian man who presented with left-side body weakness of 6 years’ duration with worsening of symptoms of 6 months’ duration. He had no history of trauma, meningitis, or previous surgery. The results of routine laboratory tests were normal. The diagnosis was made by computed tomography and magnetic resonance imaging and was confirmed by surgery. Frontoparietal craniotomy was performed, and evacuation of non-foul-smelling collection was done. The patient was reoperated for tension pneumocephalus 48 hours after the initial surgery. He died 10 days later.

Conclusion

This is a rare case of a giant chronic calcified subdural empyema with no known preceding history of trauma or infection.
Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis
Authors: He Lei , He Tianwei , Xing Jianghao , Zhou Qing , Fan Lei , Liu Can , Chen Yuyong , Wu Depeng , Tian Zhenming , Liu Bin , Rong Limin
Published: July 2020

Background

This study aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosome injection on cartilage damage and pain relief in both in vitro and in vivo models of osteoarthritis (OA).

Methods

The BMSCs were extracted from rat bone marrow of the femur and tibia. Chondrocytes were treated with IL-1β to establish the in vitro model of OA. Chondrocyte proliferation and migration were assessed by CCK-8 and transwell assay, respectively. A rat model of OA was established by injection of sodium iodoacetate. At 6 weeks after the model was established, the knee joint specimens and dorsal root ganglion (DRG) of rats were collected for histologic analyses. For pain assessment, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were evaluated before model establishment and at 1, 2, 4, and 6 weeks after model establishment.

Results

Exosomes can be endocytosed with the chondrocytes in vitro. Exosome treatment significantly attenuated the inhibitory effect of IL-1β on the proliferation and migration of chondrocytes. Exosome pre-treatment significantly attenuated IL-1β-induced downregulation of COL2A1 and ACAN and upregulation of MMP13 and ADAMTS5. In the animal study, exosome treatment significantly upregulated COL2A1 protein and downregulated MMP13 protein in the cartilage tissue of the OA rat. At weeks 2, 4, and 6, the PWL value was significantly improved in the exosome-treated OA rats as compared with the untreated OA animals. Moreover, exosome treatment significantly alleviated the upregulation of CGRP and iNOS in the DRG tissue of OA rats.

Conclusion

BMSC-derived exosomes can effectively promote cartilage repair and extracellular matrix synthesis, as well as alleviate knee pain in the OA rats.