bluuebunny/crossref_metadata_2025 huggingface dataset:
Three chemotypes of thyme (Thymus vulgaris L.) essential oil and their main compounds affect differently the IL-6 and TNFα cytokine secretions of BV-2 microglia by modulating the NF-κB and C/EBPβ signalling pathways
Authors: Horváth Györgyi , Horváth Adrienn , Reichert Gréta , Böszörményi Andrea , Sipos Katalin , Pandur Edina
Published: May 2021

Background

The essential oils possess both antimicrobial and anti-inflammatory effects, therefore they can provide an effective treatment against infections. Essential oils are widely used as supportive ingredients in many diseases, especially in the acute and chronic diseases of the respiratory tract. Neuroinflammation is responsible for several diseases of the central nervous system. Some plant-derived bioactive molecules have been shown to have role in attenuating neuroinflammation by regulating microglia, the immune cells of the CNS.

Methods

In this study, the anti-inflammatory effect of three chemotypes of thyme essential oil and their main compounds (geraniol, thujanol and linalool) were examined on lipopolysaccharide-induced BV-2 microglia. Three different experimental setups were used, LPS pretreatment, essential oil pretreatment and co-treatments of LPS and essential oils in order to determine whether essential oils are able to prevent inflammation and can decrease it. The concentrations of the secreted tumour necrosis factor α (TNFα) and interleukin-6 (IL-6) proinflammatory cytokines were measured and we analysed by Western blot the activity of the cell signalling pathways, NF-κB and CCAAT-enhancer binding protein β (C/EBPβ) regulating TNFα and IL-6 proinflammatory cytokine expressions in BV-2 cells.

Results

Our results showed definite alterations in the effects of essential oil chemotypes and their main compounds at the different experimental setups. Considering the changes of IL-6 and TNFα secretions the best reduction of inflammatory cytokines could be reached by the pretreatment with the essential oils. In addition, the main compounds exerted better effects than essential oil chemotypes in case of LPS pretreatment. At the essential oil pretreatment experiment, the effect of linalool and geraniol was outstanding but there was no major difference between the actions of chemotypes and standards. Main compounds could be seen to have large inhibitory effects on certain cell signalling components related to the activation of the expression of proinflammatory cytokines.

Conclusion

Thyme essential oils are good candidates to use in prevention of neuroinflammation and related neurodegeneration, but the exact ratio of the components has to be selected carefully.
Challenges in PhD education due to COVID-19 - disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students
Authors: Börgeson Emma , Sotak Matus , Kraft Jamie , Bagunu Grace , Biörserud Christina , Lange Stephan
Published: May 2021

Background

It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data.

Methods

An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support.

Results

PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups.

Conclusions

It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor’s emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.
Characterization and selection of Japanese electronic health record databases used as data sources for non-interventional observational studies
Authors: Wakabayashi Yumi , Eitoku Masamitsu , Suganuma Narufumi
Published: May 2021

Background

Interventional studies are the fundamental method for obtaining answers to clinical questions. However, these studies are sometimes difficult to conduct because of insufficient financial or human resources or the rarity of the disease in question. One means of addressing these issues is to conduct a non-interventional observational study using electronic health record (EHR) databases as the data source, although how best to evaluate the suitability of an EHR database when planning a study remains to be clarified. The aim of the present study is to identify and characterize the data sources that have been used for conducting non-interventional observational studies in Japan and propose a flow diagram to help researchers determine the most appropriate EHR database for their study goals.

Methods

We compiled a list of published articles reporting observational studies conducted in Japan by searching PubMed for relevant articles published in the last 3 years and by searching database providers’ publication lists related to studies using their databases. For each article, we reviewed the abstract and/or full text to obtain information about data source, target disease or therapeutic area, number of patients, and study design (prospective or retrospective). We then characterized the identified EHR databases.

Results

In Japan, non-interventional observational studies have been mostly conducted using data stored locally at individual medical institutions (663/1511) or collected from several collaborating medical institutions (315/1511). Whereas the studies conducted with large-scale integrated databases (330/1511) were mostly retrospective (73.6%), 27.5% of the single-center studies, 47.6% of the multi-center studies, and 73.7% of the post-marketing surveillance studies, identified in the present study, were conducted prospectively. We used our findings to develop an assessment flow diagram to assist researchers in evaluating and choosing the most suitable EHR database for their study goals.

Conclusions

Our analysis revealed that the non-interventional observational studies were conducted using data stored local at individual medical institutions or collected from collaborating medical institutions in Japan. Disease registries, disease databases, and large-scale databases would enable researchers to conduct studies with large sample sizes to provide robust data from which strong inferences could be drawn.
Evaluation of the accuracy of diagnostic coding for influenza compared to laboratory results: the availability of test results before hospital discharge facilitates improved coding accuracy
Authors: Wabe Nasir , Li Ling , Lindeman Robert , Post Jeffrey J. , Dahm Maria R. , Li Julie , Westbrook Johanna I. , Georgiou Andrew
Published: May 2021

Background

Assessing the accuracy of diagnostic coding is essential to ensure the validity and reliability of administrative coded data. The aim of the study was to evaluate the accuracy of assigned International Classification of Diseases version 10-Australian Modification (ICD-10-AM) codes for influenza by comparing with patients’ results of their polymerase chain reaction (PCR)-based laboratory tests.

Method

A retrospective study was conducted across seven public hospitals in New South Wales, Australia. A total of 16,439 patients who were admitted and tested by either cartridge-based rapid PCR or batched multiplex PCR between January 2016 and December 2017 met the inclusion criteria. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICD-10-AM coding using laboratory results as a gold standard. Separate analyses were conducted to determine whether the availability of test results at the time of hospital discharge influenced diagnostic coding accuracy.

Results

Laboratory results revealed 2759 positive influenza cases, while ICD-10-AM coding identified 2527 patients. Overall, 13.7% (n = 378) of test positive patients were not assigned an ICD-10-AM code for influenza. A further 5.8% (n = 146) patients with negative test results were incorrectly assigned an ICD-10-AM code for influenza. The sensitivity, specificity, PPV and NPV of ICD-10-AM coding were 93.1%; 98.9%; 94.5% and 98.6% respectively when test results were received before discharge and 32.7%; 99.2%; 87.8% and 89.8% respectively when test results were not available at discharge. The sensitivity of ICD-10-AM coding varied significantly across hospitals. The use of rapid PCR or hospitalisation during the influenza season were associated with greater coding accuracy.

Conclusion

Although ICD-10-AM coding for influenza demonstrated high accuracy when laboratory results were received before discharge, its sensitivity was substantially lower for patients whose test results were not available at discharge. The timely availability of laboratory test results during the episode of care could contribute to improved coding accuracy.
Enhancing generic capabilities and metacognitive awareness of first-year nursing students using active learning strategy
Authors: Chan Carmen Wing Han , Tang Fiona Wing Ki , Chow Ka Ming , Wong Cho Lee
Published: May 2021

Background

Developing students’ generic capabilities is a major goal of university education as it can help to equip students with life-long learning skills and promote holistic personal development. However, traditional didactic teaching has not been very successful in achieving this aim. Kember and Leung’s Teaching and Learning Model suggests an interactive learning environment has a strong impact on developing students’ generic capabilities. Metacognitive awareness is also known to be related to generic capability development. This study aimed to assess changes on the development of generic capabilities and metacognitive awareness after the introduction of active learning strategy among nursing students.

Methods

This study adopted a quasi-experimental single group, matched pre- and posttest design. It was conducted in a school of nursing at a university in Hong Kong. Active learning approaches included the flipped classroom (an emphasis on pre-reading) and enhanced lectures (the breaking down of a long lecture into several mini-lectures and supplemented by interactive learning activities) were introduced in a foundational nursing course. The Capabilities Subscale of the Student Engagement Questionnaire and the Metacognitive Awareness Inventory were administered to two hundred students at the start (T0) and at the end of the course (T1). A paired t-test was performed to examine the changes in general capabilities and metacognitive awareness between T0 and T1.

Results

A total of 139 paired pre- and post-study responses (69.5 %) were received. Significant improvements were observed in the critical thinking (p < 0.001), creative thinking (p = 0.03), problem-solving (p < 0.001) and communication skills (p = 0.04) with the implementation of active learning. Significant changes were also observed in knowledge of cognition (p < 0.001) and regulation of cognition (p < 0.001) in the metacognitive awareness scales.

Conclusions

Active learning is a novel and effective teaching approach that can be applied in the nursing education field. It has great potential to enhance students’ development of generic capabilities and metacognitive awareness.
Healthcare beliefs and practices of kin caregivers in South Africa: implications for child survival
Authors: Mabetha Khuthala , De Wet-Billings Nicole C. , Odimegwu Clifford O.
Published: May 2021

Background

Appropriate health-seeking practices may have a positive influence on child survival, particularly when practiced by kin caregivers of children who are below the age of 5 years. While literature has shown that children who are raised in kinship care often present with poor health outcomes and often have unmet healthcare needs, the health-seeking behaviours and practices of the children’s kin caregivers that ultimately influence these health outcomes remain largely unknown. In this paper, we explored the healthcare beliefs and practices of kin caregivers in South Africa on child survival.

Methods

Overall, 12 structured interviews were conducted with all the participants. Six [6] interviews were conducted in the Eastern Cape province and 6 were conducted in the KwaZulu-Natal province. The sample of participants was obtained by seeking permission from the child welfare authorities in the KwaZulu-Natal and Eastern Cape Department of Social Development (DSD) to assist in identifying a sample of the kin-caregivers who have provided primary care to children below the age of 5. The structured interviews were transcribed and analysed using thematic content analysis. After thematic content analysis was carried out, transcripts were given case numbers and then imported into NViVo version 11 for analysis and interpretation of the findings.

Results

The healthcare seeking behaviours and poor use of healthcare services of the caregivers were largely influenced by their notions and perceptions of health and illness. The notions and perceptions that the caregivers hold about the health statuses of the children placed under their care and illness were found to be largely culturally determined and largely influenced by preconceptions and certain healthcare beliefs. Increased reliance on traditional herbs, Notion of witchcraft and Faith healing emerged as key factors that influence health-seeking practices and beliefs of kin caregivers, thus influencing under-five mortality.

Conclusion

Kin caregivers should be equipped with the necessary guidance, resources and training that facilitate the successful fulfilment of the caregiving role, given the number of unmet needs and challenges that they face. This will in turn translate into positive child health outcomes.
Towards a standardized approach of assessing social context of persons receiving home care in Flanders, Belgium: the development and test of a social supplement to the interRAI instruments
Authors: Van Doren Shauni , Hermans Kirsten , Declercq Anja
Published: May 2021

Background

Apart from a person’s physical functioning, the early identification of social context indicators which affect patient outcomes - such as environmental and psychosocial issues - is key for high quality and comprehensive care at home. During a home care assessment, a person’s biomedical and functional problems are typically considered. Harder to define concepts, such as psychosocial well-being or living arrangements, are not routinely documented, even though research shows they also affect functioning and health outcomes. The purpose of this study is to develop and test a concise, integrated assessment (BelRAI Social Supplement) that evaluates these social context indicators for persons receiving home care to complement existing interRAI- instruments.

Methods

The development of the BelRAI Social Supplement is a multi-stage process, based upon the revised MRC-framework, involving both qualitative and quantitative research with stakeholders such as; clients, informal caregivers, care professionals and policy makers. The developmental process encompasses four stages: (I) item generation based on multiple methods and content validation by a panel of stakeholders (II) assessing feasibility and piloting methods, (III) early evaluation, and (IV) final evaluation. Stage II and III are covered in this paper.

Results

During Stages I and II, a testable version of the BelRAI Social Supplement was developed in an iterative process. In Stage III, 100 care professionals assessed 743 individuals receiving home care in Flanders between December 2018 and December 2019. Using inter-item correlation matrixes, frequency distributions and regular feedback from the participants, the BelRAI Social Supplement was improved and prepared for Stage IV. The updated version of the instrument consists of four main sections: (1) environmental assessment; (2) civic engagement; (3) psychosocial well-being; and (4) informal care and support. In total, the BelRAI Social Supplement contains a maximum of 76 items.

Conclusions

The BelRAI Social Supplement was reviewed and shortened in close collaboration with care professionals and other experts in Flanders. This study resulted in an instrument that documents need-to-know social context determinants of home dwelling adults.
Patient volume and quality of primary care in Ethiopia: findings from the routine health information system and the 2014 Service Provision Assessment survey
Authors: Arsenault Catherine , Yakob Bereket , Tilahun Tizta , Nigatu Tsinuel Girma , Dinsa Girmaye , Woldie Mirkuzie , Kassa Munir , Berman Peter , Kruk Margaret E.
Published: May 2021

Background

Several studies have reported inadequate levels of quality of care in the Ethiopian health system. Facility characteristics associated with better quality remain unclear. Understanding associations between patient volumes and quality of care could help organize service delivery and potentially improve patient outcomes.

Methods

Using data from the routine health management information system (HMIS) and the 2014 Ethiopian Service Provision Assessment survey + we assessed associations between daily total outpatient volumes and quality of services. Quality of care at the facility level was estimated as the average of five measures of provider knowledge (clinical vignettes on malaria and tuberculosis) and competence (observations of family planning, antenatal care and sick child care consultations). We used linear regression models adjusted for several facility-level confounders and region fixed effects with log-transformed patient volume fitted as a linear spline. We repeated analyses for the association between volume of antenatal care visits and quality.

Results

Our analysis included 424 facilities including 270 health centers, 45 primary hospitals and 109 general hospitals in Ethiopia. Quality was low across all facilities ranging from only 18 to 56% with a mean score of 38%. Outpatient volume varied from less than one patient per day to 581. We found a small but statistically significant association between volume and quality which appeared non-linear, with an inverted U-shape. Among facilities seeing less than 90.6 outpatients per day, quality increased with greater patient volumes. Among facilities seeing 90.6 or more outpatients per day, quality decreased with greater patient volumes. We found a similar association between volume and quality of antenatal care visits.

Conclusions

Health care utilization and quality must be improved throughout the health system in Ethiopia. Our results are suggestive of a potential U-shape association between volume and quality of primary care services. Understanding the links between volume of patients and quality of care may provide insights for organizing service delivery in Ethiopia and similar contexts.
The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens
Authors: Hatefi Ali , Zare Shahneh Ahmad , Ansari Pirsaraie Zarbakht , Alizadeh Ali Mohammad , Atashnak Mohammad Pouya , Masoudi Reza , Pio Frederic
Published: May 2021

Background

Ovarian chronic inflammation has been known to incidence in the laying hen mainly via increasing laying frequency and microbial infection, especially during late stage of production period. This study was aimed to evaluate beta-2 adrenergic agonist (Beta-2 Adrenergic Agonist, BAA) Salmeterol and beta blocker (Beta Blocker, BB) Propranolol on the gene expression of the ovarian pro- and anti-inflammatory mediators, inflammatory responses of immune system, ovarian functions and, hormones in the laying hens on the late stage of production period. Forty-eight White Leghorn hens aged 92 weeks were used for 4 weeks to be supplemented by Salmeterol and Propranolol. Ovulation rate and follicular growth were determined based on laying frequency and ovarian visual evaluation, respectively; the mRNA expressions of follicular beta-2 adrenergic receptor (Beta-2 Adrenergic Receptor, β2ADR), cyclooxygenases (Cyclooxygenases, COX) 1 and 2, and cytokines were measured by real-time PCR. The plasma concentration of ovarian hormones, cellular, and humoral immune responses were measured via ELISA, heterophil to lymphocyte ratio (Heterophil to Lymphocyte ratio, H:L), and sheep red blood cell (Sheep Red Blood Cell, SRBC) test, respectively.

Results

As compared to control, both of BAA Salmeterol and BB Propranolol resulted in a significant decrease in the mRNA expression of β2ADR, cyclooxygenases, and pro- and anti-inflammatory cytokines (P < 0.01). A significant elevation was observed in the ovulation rate (P < 0.05), plasma estradiol content on both treated groups (P < 0.05), and the content of progesterone and was just significantly (P < 0.05) increased in Salmeterol group. H:L was reduced in BAA group (P < 0.05), and immunoglobulin (Ig) M was elevated in both treated hens, when compared to control. The results indicated that Salmeterol significantly increases body weight (P < 0.05).

Conclusion

The stimulation and inhibition of beta-2 adrenergic signaling could reduce ovarian inflammatory condition in addition to enhancing laying efficiency in the aged laying hens.
Genomic trajectory in leukemogenesis of myeloproliferative neoplasms: a case report
Authors: Chen Yujie , Talukder Rafee , Merritt Brian Y. , King Katherine Y. , Kimmel Marek , Rivero Gustavo , Sosa Romina
Published: May 2021

Background

We report a patient with Essential Thrombocythemia (ET), subsequently diagnosed with concurrent myeloid and lymphoid leukemia. Generally, the molecular mechanisms underlying leukemic transformation of Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are poorly understood. Risk of transformation to acute myelogenous leukemia (AML) is low; transformation to both AML and acute lymphoblastic leukemia (ALL) is extremely low. Genetic defects, including allele burden, order of mutation acquisition, clonal heterogeneity and epigenetic mechanisms are important contributors to disease acceleration.

Case presentation

A 78-year-old Caucasian female originally treated for stable ET, underwent disease acceleration and transition to myeloid sarcoma and B-cell ALL. Genomic reconstruction based on targeted sequencing revealed the presence of a large del(5q) in all three malignancies and somatic driver mutations:TET2, TP53,SF3B1, andASXL1at high allele frequency. We propose that the combination of genetic and molecular abnormalities led to hematopoietic stem cell (HSC) injury and disease progression through sub-clone branching. We hypothesize that ancestral reconstruction of genomic data is a useful tool to uncover subclonal events leading to transformation.

Conclusions

The use of ancestral reconstruction of genomic data sheds light on the unique clinical scenario described in this case report. By determining the mutational profile of tumors at several timepoints and deducing the most parsimonious relationship between them, we propose a reconstruction of their origin. We propose that blast progression originated from subclonal events with malignant potential, which coexisted with but did not originate fromJAK2 p.V617F-positive ET. We conclude that the application of genomic reconstruction enhances our understanding of leukemogenesis by identifying the timing of molecular events, potentially leading to better chemotherapy choices as well as the development of new targeted therapies.
Microbiota identified from preserved Anopheles
Authors: E Silva Bianca , Matsena Zingoni Zvifadzo , Koekemoer Lizette L. , Dahan-Moss Yael L.
Published: May 2021

Background

Mosquito species from the Anopheles gambiae complex and the Anopheles funestus group are dominant African malaria vectors. Mosquito microbiota play vital roles in physiology and vector competence. Recent research has focused on investigating the mosquito microbiota, especially in wild populations. Wild mosquitoes are preserved and transported to a laboratory for analyses. Thus far, microbial characterization post-preservation has been investigated in only Aedes vexans and Culex pipiens. Investigating the efficacy of cost-effective preservatives has also been limited to AllProtect reagent, ethanol and nucleic acid preservation buffer. This study characterized the microbiota of African Anopheles vectors: Anopheles arabiensis (member of the An. gambiae complex) and An. funestus (member of the An. funestus group), preserved on silica desiccant and RNAlater® solution.

Methods

Microbial composition and diversity were characterized using culture-dependent (midgut dissections, culturomics, MALDI-TOF MS) and culture-independent techniques (abdominal dissections, DNA extraction, next-generation sequencing) from laboratory (colonized) and field-collected mosquitoes. Colonized mosquitoes were either fresh (non-preserved) or preserved for 4 and 12 weeks on silica or in RNAlater®. Microbiota were also characterized from field-collected An. arabiensis preserved on silica for 8, 12 and 16 weeks.

Results

Elizabethkingia anophelis and Serratia oryzae were common between both vector species, while Enterobacter cloacae and Staphylococcus epidermidis were specific to females and males, respectively. Microbial diversity was not influenced by sex, condition (fresh or preserved), preservative, or preservation time-period; however, the type of bacterial identification technique affected all microbial diversity indices.

Conclusions

This study broadly characterized the microbiota of An. arabiensis and An. funestus. Silica- and RNAlater®-preservation were appropriate when paired with culture-dependent and culture-independent techniques, respectively. These results broaden the selection of cost-effective methods available for handling vector samples for downstream microbial analyses.
Determinants of intermittent preventive treatment with sulfadoxine–pyrimethamine in pregnant women (IPTp-SP) in Mali, a household survey
Authors: Sangho Oumar , Tounkara Moctar , Whiting-Collins Lillian Joyce , Beebe Madeleine , Winch Peter J. , Doumbia Seydou
Published: May 2021

Background

In malaria endemic regions, intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is recommended for all pregnant women during prenatal consultation, from the fourth month of pregnancy up to the time of delivery. The Government of Mali is aiming for universal coverage of IPTp-SP. However, coverage is still low, estimated to be 18% for completion of three doses (IPTp-SP3). The objective of this study was to identify the factors that influence IPTp-SP adherence in the Health District of Sélingué, Mali.

Methods

This was a cross-sectional survey with 30 clusters, proportional to village size, with two stages of sampling. Data were collected electronically with Magpi software during face-to-face interviews/surveys. The data were analysed with SPSS version 20. A descriptive analysis and bivariate and multivariate logistic regression were performed. An equity analysis examined the effect of distance from health care facility on completion of three or more antenatal visits (ANC3 +) and three or more doses of intermittent preventive treatment (IPTp-SP3 +).

Results

Of the 1,021 women surveyed, 87.8% (n = 896) attended at least one ANC visit. Of these, 86.3% (n = 773) received at least one dose of IPTp-SP. Compliance with three or more doses of IPTp-SP was 63.7%. The determinants statistically related to ANC3 + were the early initiation of ANC (OR = 3.22 [1.22, 10.78]), and the presence of a community health centre (CHC) in the village (OR = 9.69 [1.09, 86.21]). The ability to read (OR = 1.60 [1.01, 2.55]), the early initiation of ANC (OR = 1.46 [1.06, 2.00], knowledge of the utility of the drug (OR = 2.38 [1.24, 4.57]), and knowledge of the recommended dose of the drug (OR = 6.11 [3.98, 9.39]) were related to completion of three or more treatments (IPTp-SP3 +).

Conclusion

The early initiation of ANC was a positive determinant of the completeness of both ANC3 + and IPTp-SP3 + . This study shows that a successful implementation of the IPTp strategy can be achieved by improving access to prenatal care at community health facilities, and strengthening patient-provider communication to ensure adequate knowledge on dosing of IPTp-SP and the benefits to mother and child.
The effect of community-driven larval source management and house improvement on malaria transmission when added to the standard malaria control strategies in Malawi: a cluster-randomized controlled trial
Authors: McCann Robert S. , Kabaghe Alinune N. , Moraga Paula , Gowelo Steven , Mburu Monicah M. , Tizifa Tinashe , Chipeta Michael G. , Nkhono William , Di Pasquale Aurelio , Maire Nicolas , Manda-Taylor Lucinda , Mzilahowa Themba , van den Berg Henk , Diggle Peter J. , Terlouw Dianne J. , Takken Willem , van Vugt Michèle , Phiri Kamija S.
Published: May 2021

Background

Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi National Malaria Control Programme (NMCP) interventions were assessed in the context of an intensive community engagement programme.

Methods

The study was a two-by-two factorial, cluster-randomized controlled trial in Malawi. Village clusters were randomly assigned to four arms: a control arm; HI; LSM; and HI + LSM. Malawi NMCP interventions and community engagement were used in all arms. Household-level, cross-sectional surveys were conducted on a rolling, 2-monthly basis to measure parasitological and entomological outcomes over 3 years, beginning with one baseline year. The primary outcome was the entomological inoculation rate (EIR). Secondary outcomes included mosquito density, Plasmodium falciparum prevalence, and haemoglobin levels. All outcomes were assessed based on intention to treat, and comparisons between trial arms were conducted at both cluster and household level.

Results

Eighteen clusters derived from 53 villages with 4558 households and 20,013 people were randomly assigned to the four trial arms. The mean nightly EIR fell from 0.010 infectious bites per person (95% CI 0.006–0.015) in the baseline year to 0.001 (0.000, 0.003) in the last year of the trial. Over the full trial period, the EIR did not differ between the four trial arms (p = 0.33). Similar results were observed for the other outcomes: mosquito density and P. falciparum prevalence decreased over 3 years of sampling, while haemoglobin levels increased; and there were minimal differences between the trial arms during the trial period.

Conclusions

In the context of high insecticide-treated bed net use, neither community-based HI, LSM, nor HI + LSM contributed to further reductions in malaria transmission or prevalence beyond the reductions observed over two years across all four trial arms. This was the first trial, as far as the authors are aware, to test the potential complementary impact of LSM and/or HI beyond levels achieved by standard interventions. The unexpectedly low EIR values following intervention implementation indicated a promising reduction in malaria transmission for the area, but also limited the usefulness of this outcome for measuring differences in malaria transmission among the trial arms.

Trial registration PACTR, PACTR201604001501493, Registered 3 March 2016, https://pactr.samrc.ac.za/.
Discrimination between healthy and patients with Parkinson’s disease from hand resting activity using inertial measurement unit
Authors: Peres Luciano Brinck , Calil Bruno Coelho , da Silva Ana Paula Sousa Paixão Barroso , Dionísio Valdeci Carlos , Vieira Marcus Fraga , de Oliveira Andrade Adriano , Pereira Adriano Alves
Published: May 2021

Background

Parkinson’s disease (PD) is a neurological disease that affects the motor system. The associated motor symptoms are muscle rigidity or stiffness, bradykinesia, tremors, and gait disturbances. The correct diagnosis, especially in the initial stages, is fundamental to the life quality of the individual with PD. However, the methods used for diagnosis of PD are still based on subjective criteria. As a result, the objective of this study is the proposal of a method for the discrimination of individuals with PD (in the initial stages of the disease) from healthy groups, based on the inertial sensor recordings.

Methods

A total of 27 participants were selected, 15 individuals previously diagnosed with PD and 12 healthy individuals. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Different numbers of features were used to compare the values of sensitivity, specificity, precision, and accuracy of the classifiers. For group classification, 4 classifiers were used and compared, those being [Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Naive Bayes (NB)].

Results

When all individuals with PD were analyzed, the best performance for sensitivity and accuracy (0.875 and 0.800, respectively) was found in the SVM classifier, fed with 20% and 10% of the features, respectively, while the best performance for specificity and precision (0.933 and 0.917, respectively) was associated with the RF classifier fed with 20% of all the features. When only individuals with PD and score 1 on the Hoehn and Yahr scale (HY) were analyzed, the best performances for sensitivity, precision and accuracy (0.933, 0.778 and 0.848, respectively) were from the SVM classifier, fed with 40% of all features, and the best result for precision (0.800) was connected to the NB classifier, fed with 20% of all features.

Conclusion

Through an analysis of all individuals in this study with PD, the best classifier for the detection of PD (sensitivity) was the SVM fed with 20% of the features and the best classifier for ruling out PD (specificity) was the RF classifier fed with 20% of the features. When analyzing individuals with PD and score HY = 1, the SVM classifier was superior across the sensitivity, precision, and accuracy, and the NB classifier was superior in the specificity. The obtained result indicates that objective methods can be applied to help in the evaluation of PD.
Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study
Authors: Kim Keewan , Pollack Anna Z. , Nobles Carrie J. , Sjaarda Lindsey A. , Zolton Jessica R. , Radoc Jeannie G. , Schisterman Enrique F. , Mumford Sunni L.
Published: May 2021

Background

Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age.

Methods

This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively.

Results

Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure.

Conclusions

Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.
Comparative evaluation of six nucleic acid amplification kits for SARS-CoV-2 RNA detection
Authors: Wu Shuang , Shi Xiaolu , Chen Qiongcheng , Jiang Yixiang , Zuo Le , Wang Lei , Jiang Min , Lin Yiman , Fang Shisong , Peng Bo , Wu Weihua , Liu Hui , Zhang Renli , Kwan Patrick S. L. , Hu Qinghua
Published: May 2021

Background

SARS-CoV-2 is a newly emerged coronavirus, causing the coronavirus disease 2019 (COVID-19) outbreak in December, 2019. As drugs and vaccines of COVID-19 remain in development, accurate virus detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) kits have been reliably used for detection of SARS-CoV-2 RNA since the beginning of the COVID-19 outbreak, whereas isothermal nucleic acid amplification-based point-of-care automated kits have also been considered as a simpler and rapid alternative. However, as these kits have only been developed and applied clinically within a short timeframe, their clinical performance has not been adequately evaluated to date. We describe a comparative study between a newly developed cross-priming isothermal amplification (CPA) kit (Kit A) and five RT-qPCR kits (Kits B–F) to evaluate their sensitivity, specificity, predictive values and accuracy.

Methods

Fifty-two clinical samples were used including throat swabs (n = 30), nasal swabs (n = 7), nasopharyngeal swabs (n = 7) and sputum specimens (n = 8), comprising confirmed (n = 26) and negative cases (n = 26). SARS-CoV-2 detection was simultaneously performed on each sample using six nucleic acid amplification kits. The sensitivity, specificity, positive/negative predictive values (PPV/NPV) and the accuracy for each kit were assessed using clinical manifestation and molecular diagnoses as the reference standard. Reproducibility for RT-qPCR kits was evaluated in triplicate by three different operators using a SARS-CoV-2 RNA-positive sample. On the basis of the six kits’ evaluation results, CPA kit (Kit A) and two RT-qPCR Kits (Kit B and F) were applied to the SARS-CoV-2 detection in close-contacts of COVID-19 patients.

Results

For Kit A, the sensitivity, specificity, PPV/NPV and accuracy were 100%. Among the five RT-qPCR kits, Kits B, C and F had good agreement with the clinical diagnostic reports (Kappa ≥ 0.75); Kits D and E were less congruent (0.4 ≤ Kappa < 0.75). Differences between all kits were statistically significant (P < 0.001). The reproducibility of RT-qPCR kits was determined using a coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility.

Conclusions

This is the first comparative study to evaluate CPA and RT-qPCR kits’ specificity and sensitivity for SARS-CoV-2 detection, and could serve as a reference for clinical laboratories, thus informing testing protocols amid the rapidly progressing COVID-19 pandemic.
RETRACTED ARTICLE: VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation
Authors: Ren Bo , Feng Que , He Shan , Li Yanfeng , Fan Jiadong , Chai Guangquan , Liu Le , Liu Haiyun , Yang Chunhao , Wang Yingdi , Liu Huihui , Liu Huanyue , Song Yafan
Published: May 2021

Background

Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis.

Methods

Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated.

Results

Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01–46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25–3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion.

Conclusions

High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.
Extracellular vesicles-based pre-targeting strategy enables multi-modal imaging of orthotopic colon cancer and image-guided surgery
Authors: Jing Boping , Qian Ruijie , Jiang Dawei , Gai Yongkang , Liu Zhen , Guo Feng , Ren Sen , Gao Yu , Lan Xiaoli , An Rui
Published: May 2021

Backgroud

Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models.

Results

Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was − 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed.

Conclusions

In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers.

Graphic Abstract
pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer
Authors: Wang He , Shi Wenwen , Zeng Danning , Huang Qiudi , Xie Jiacui , Wen Huaying , Li Jinfang , Yu Xiyong , Qin Linghao , Zhou Yi
Published: May 2021

Background

Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown.

Results

Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells.

Conclusions

These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment.

Graphic Abstarct