bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a new barcode-based, multiplex-PCR, next-generation-sequencing assay and data processing and analytical pipeline for multiplicity of infection detection of Plasmodium falciparum
Authors: Mitchell Rebecca M. , Zhou Zhiyong , Sheth Mili , Sergent Sheila , Frace Michael , Nayak Vishal , Hu Bin , Gimnig John , ter Kuile Feiko , Lindblade Kim , Slutsker Laurence , Hamel Mary J. , Desai Meghna , Otieno Kephas , Kariuki Simon , Vigfusson Ymir , Shi Ya Ping
Published: February 2021

Background

Simultaneous infection with multiple malaria parasite strains is common in high transmission areas. Quantifying the number of strains per host, or the multiplicity of infection (MOI), provides additional parasite indices for assessing transmission levels but it is challenging to measure accurately with current tools. This paper presents new laboratory and analytical methods for estimating the MOI of Plasmodium falciparum.

Methods

Based on 24 single nucleotide polymorphisms (SNPs) previously identified as stable, unlinked targets across 12 of the 14 chromosomes within P. falciparum genome, three multiplex PCRs of short target regions and subsequent next generation sequencing (NGS) of the amplicons were developed. A bioinformatics pipeline including B4Screening pathway removed spurious amplicons to ensure consistent frequency calls at each SNP location, compiled amplicons by SNP site diversity, and performed algorithmic haplotype and strain reconstruction. The pipeline was validated by 108 samples generated from cultured-laboratory strain mixtures in different proportions and concentrations, with and without pre-amplification, and using whole blood and dried blood spots (DBS). The pipeline was applied to 273 smear-positive samples from surveys conducted in western Kenya, then providing results into StrainRecon Thresholding for Infection Multiplicity (STIM), a novel MOI estimator.

Results

The 24 barcode SNPs were successfully identified uniformly across the 12 chromosomes of P. falciparum in a sample using the pipeline. Pre-amplification and parasite concentration, while non-linearly associated with SNP read depth, did not influence the SNP frequency calls. Based on consistent SNP frequency calls at targeted locations, the algorithmic strain reconstruction for each laboratory-mixed sample had 98.5% accuracy in dominant strains. STIM detected up to 5 strains in field samples from western Kenya and showed declining MOI over time (q < 0.02), from 4.32 strains per infected person in 1996 to 4.01, 3.56 and 3.35 in 2001, 2007 and 2012, and a reduction in the proportion of samples with 5 strains from 57% in 1996 to 18% in 2012.

Conclusion

The combined approach of new multiplex PCRs and NGS, the unique bioinformatics pipeline and STIM could identify 24 barcode SNPs of P. falciparum correctly and consistently. The methodology could be applied to field samples to reliably measure temporal changes in MOI.
Development and evaluation of a new Plasmodium falciparum 3D7 blood stage malaria cell bank for use in malaria volunteer infection studies
Authors: Woolley Stephen D. , Fernandez Melissa , Rebelo Maria , Llewellyn Stacey A. , Marquart Louise , Amante Fiona H. , Jennings Helen E. , Webster Rebecca , Trenholme Katharine , Chalon Stephan , Moehrle Joerg J. , McCarthy James S. , Barber Bridget E.
Published: February 2021

Background

New anti-malarial therapeutics are required to counter the threat of increasing drug resistance. Malaria volunteer infection studies (VIS), particularly the induced blood stage malaria (IBSM) model, play a key role in accelerating anti-malarial drug development. Supply of the reference 3D7-V2 Plasmodium falciparum malaria cell bank (MCB) is limited. This study aimed to develop a new MCB, and compare the safety and infectivity of this MCB with the existing 3D7-V2 MCB, in a VIS. A second bank (3D7-V1) developed in 1995 was also evaluated.

Methods

The 3D7-V2 MCB was expanded in vitro using a bioreactor to produce a new MCB designated 3D7-MBE-008. This bank and 3D7-V1 were then evaluated using the IBSM model, where healthy participants were intravenously inoculated with blood-stage parasites. Participants were treated with artemether-lumefantrine when parasitaemia or clinical thresholds were reached. Safety, infectivity and parasite growth and clearance were evaluated.

Results

The in vitro expansion of 3D7-V2 produced 200 vials of the 3D7-MBE-008 MCB, with a parasitaemia of 4.3%. This compares to 0.1% in the existing 3D7-V2 MCB, and < 0.01% in the 3D7-V1 MCB. All four participants (two per MCB) developed detectable P. falciparum infection after inoculation with approximately 2800 parasites. For the 3D7-MBE-008 MCB, the parasite multiplication rate of 48 h (PMR48) using non-linear mixed effects modelling was 34.6 (95% CI 18.5–64.6), similar to the parental 3D7-V2 line; parasitaemia in both participants exceeded 10,000/mL by day 8. Growth of the 3D7-V1 was slower (PMR48 of 11.5 [95% CI 8.5–15.6]), with parasitaemia exceeding 10,000 parasites/mL on days 10 and 8.5. Rapid parasite clearance followed artemether-lumefantrine treatment in all four participants, with clearance half-lives of 4.01 and 4.06 (weighted mean 4.04 [95% CI 3.61–4.57]) hours for 3D7-MBE-008 and 4.11 and 4.52 (weighted mean 4.31 [95% CI 4.16–4.47]) hours for 3D7-V1. A total of 59 adverse events occurred; most were of mild severity with three being severe in the 3D7-MBE-008 study.

Conclusion

The safety, growth and clearance profiles of the expanded 3D7-MBE-008 MCB closely resemble that of its parent, indicating its suitability for future studies. Trial Registration: Australian New Zealand Clinical Trials registry numbers: P3487 (3D7-V1): ACTRN12619001085167. P3491 (3D7-MBE-008): ACTRN12619001079134
miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools
Authors: Galvão-Lima Leonardo J. , Morais Antonio H. F. , Valentim Ricardo A. M. , Barreto Elio J. S. S.
Published: February 2021

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with the regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. This paper presents a systematic review of literature of miRNAs related to cancer development and explores the main techniques used to quantify these molecules and their limitations as screening strategy. The bibliographic research was conducted using the online databases, PubMed, Google Scholar, Web of Science, and Science Direct searching the terms “microRNA detection”, “miRNA detection”, “miRNA and prostate cancer”, “miRNA and cervical cancer”, “miRNA and cervix cancer”, “miRNA and breast cancer”, and “miRNA and early cancer diagnosis”. Along the systematic review over 26,000 published papers were reported, and 252 papers were returned after applying the inclusion and exclusion criteria, which were considered during this review. The aim of this study is to identify potential miRNAs related to cancer development that may be useful for early cancer diagnosis, notably in the breast, prostate, and cervical cancers. In addition, we suggest a preliminary top 20 miRNA panel according to their relevance during the respective cancer development. Considering the progressive number of new cancer cases every year worldwide, the development of new diagnostic tools is critical to refine the accuracy of screening tests, improving the life expectancy and allowing a better prognosis for the affected patients.
Multi-carbon dots and aptamer based signal amplification ratiometric fluorescence probe for protein tyrosine kinase 7 detection
Authors: Ma Yunsu , Wang Yuan , Liu Yongjie , Shi Lujia , Yang Dongzhi
Published: February 2021

Background

Protein tyrosine kinase 7 (PTK 7) is a membrane receptor, which can be found in various kinds of cancers. In view of this, detection of PTK 7 in the peripheral circulation would be an effective way for the early diagnosis of cancer.

Results

In this work, a multi-carbon dots and aptamer-based signal amplification ratiometric fluorescence probe was developed. The fluorescence of the aptamer-modified y-CDs and b-CDs were respectively chosen as the detection signal and interior label. The fluorescence of y-CDs was quenched by Fe3O4 and cDNA (complement to aptamer) compound without PTK 7, but recovered by the addition of PTK 7. Then, the free aptamer was cut by DNase I, which amplified the detection signal. The ratiometric fluorescence sensor for PTK 7 was established with the LOD of 0.016 ng mL−1.

Conclusions

Summary, a multi-carbon dots and aptamer-based signal amplification ratiometric fluorescence probe was developed for the detection of protein tyrosine kinase 7. The developed probe was applied to PTK 7 detection in MCF-7 cells and human serum with satisfying results, thus indicating that this probe has huge potential in clinical practice.
Nanochitin whisker enhances insecticidal activity of chemical pesticide for pest insect control and toxicity
Authors: Li Zhenya , Wang Hezhong , An Shiheng , Yin Xinming
Published: February 2021

Background

Nanomaterials in plant protection promise many benefits over conventional pesticide products. Nano-enabled pesticides may alter the functionality or risk profile of active ingredients. Cationic nanochitin whiskers (NC) possess strong biological activity against wheat aphids. However, toxicity and synergistic effects of NC with chemical pesticides against pest insects has not been systemically reported. This study investigated the insecticidal enhancement by NC with Omethoate (40% EC), Imidacloprid (10% WP), and Acetamiprid (40% WG) for pest control using wheat aphid as piercing-sucking mouthparts insect. Fluorescein isothiocyanate labelled NC was used to monitor the uptake and transportation pathway of NC inside the target insects. Toxicity of NC was tested with Sprague-Dawley (SD) rat. Our findings provide a theoretical basis for future application of NC in plant protection against pest insects.

Results

NCs synthesized by acidic hydrolysis were rod-like nanoparticles in a range of 50–150 nm in length and 30–50 nm in width, which examined by electron microscopy and dynamic light scattering methods. The charge density and zeta potential were about 63 mmol/kg and + 36.4 mV, respectively. By absorption and/or contact action of 30–50 mg/L of NC suspension, the corrected mortality of wheat aphids reached up to 80% or above after 12 h treatment, NC could be distributed through digestive system and relocated from mouth to other tissues inside the insect body. When associated with dilutions of conventional pesticides, the corrected mortality were significantly increased up to 95% or above. The dosage of the chemical pesticide and nanochitin in the mixtures (1:1 by volume) were all reduced to half. The acute oral toxicity Lethal Dose 50% (LD50) to SD rat is greater than 5000 mg/kg BW (body weight) in male and female, acute dermal toxicity LD50 is greater than 2000 mg/kg BW of NC.

Conclusions

NC has a strong promotive effect on insecticidal effectiveness of chemical insecticides. It was easily absorbed by plant, transported and distributed from mouth to other tissues of the insects while sucking plant fluid. Low acute oral and dermal toxicity to SD rat indicated that it is safe to apply in agriculture and food industry. NCs has a great potential for water-based nanopesticide formulation to reduce chemical pesticide use for future agro-environmental sustainability.
Peer support workers as a bridge: a qualitative study exploring the role of peer support workers in the care of people who use drugs during and after hospitalization
Authors: Lennox Robin , Lamarche Larkin , O’Shea Tim
Published: February 2021

Background

To describe the key qualities and unique roles of peer support workers in the care of people who inject drugs during and after hospitalization.

Methods

We conducted a qualitative study. Key stakeholders were recruited including: people who use drugs who had been hospitalized, healthcare team members, peer support workers, and employers of peer support workers. Data were collected from 2019 to 2020 using semi-structured interviews that were audio-recorded, transcribed, and analyzed thematically.

Results

Fourteen participants were interviewed: 6 people who use drugs who had been hospitalized, 5 healthcare team members, 2 peer support workers, and 1 employer of peer support workers. At the core of the data was the notion of peer workers acting as a bridge. We found four themes that related to functions of this bridge: overcoming system barriers, advocacy, navigating transitions within the healthcare system, and restoring trust between HCPs and PWUD. We found two themes for building a strong bridge and making the role of a peer support worker function effectively (training and mentorship, and establishing boundaries). We found three themes involving characteristics of an effective peer worker (intrinsic qualities, contributions of shared experiences, and personal stability).

Conclusion

Peer support workers are highly valued by both people who use drugs and members of the healthcare team. Peer support workers act as a bridge between patients and healthcare providers and are critical in establishing trust, easing transitions in care, and providing unique supports to people who use drugs during and after hospitalization.
Attachment: the mediating role of hope, religiosity, and life satisfaction in older adults
Authors: Pahlevan Sharif Saeed , Amiri Mohammadreza , Allen Kelly-Ann , Sharif Nia Hamid , Khoshnavay Fomani Fatemeh , Hatef Matbue Yasaman , Goudarzian Amir Hossein , Arefi Sedigheh , Yaghoobzadeh Ameneh , Waheed Hassam
Published: February 2021

Background

Attachment and support from family and friends are core to the experiences of ageing for older adults. The purpose of this study is to examine the relationships between attachment styles and hope, religiosity, and life satisfaction and provide new knowledge that may assist future planning for a rapidly ageing global population.

Methods

In this cross-sectional study, 504 Iranian older adult participants from Qazvin province were recruited between December 2015 and April 2016. They completed a questionnaire that included the Revised Adult Attachment Scale, the Life Satisfaction Index-Z, and the Herth Hope Index.

Results

Participants in the study had a mean age of 66.20 years (SD: 5.76) and most of them were women (57.5%). A mediation model testing the direct relationships between attachment, hope, religiosity, and life satisfaction showed a positive relationship between close attachment and religiosity (β = .226, p < .001) and a negative relationship between anxiety attachment and religiosity (β =  − .229, p < .001). Religiosity was positively related to hope (β = .384, p < .01) and hope was related to life satisfaction (β = .448, p < .001). Religiosity and hope mediated the relationship between close attachment (β = .119, p < .001) and anxiety attachment (β =  − .056, p < .01) with life satisfaction. More specifically, while religiosity and hope fully mediated the relationship between close attachment and life satisfaction, they partially mediated the attachment anxiety-life satisfaction link.

Conclusions

Findings of the study provide insight into only a narrow perspective of life satisfaction and attachment given the many and varied variables that influence these constructs. Future research is needed whereby other related variables are introduced into the model to be examined further.
Nurses in advanced roles as a strategy for equitable access to healthcare in the WHO Western Pacific region: a mixed methods study
Authors: Kim Sue , Lee Tae Wha , Kim Gwang Suk , Cho Eunhee , Jang Yeonsoo , Choi Mona , Baek Seoyoung , Lindsay David , Chan Sally , Lee Regina L. T. , Guo Aimin , Wong Frances Kam Yuet , Yu Doris , Chair Sek Ying , Shimpuku Yoko , Mashino Sonoe , Lim Gigi , Bonito Sheila , Rumsey Michele , Neill Amanda , Hazarika Indrajit
Published: February 2021

Background

The Western Pacific region constitutes one-quarter of the world’s population and has diverse health needs. While dialogue on and promotion of advanced practice nurses are ongoing, this study investigated the current responsibilities of nurses in advanced roles, future healthcare needs, and the implications of these components for nurses’ professional development within the Western Pacific region.

Methods

This study employed three phases, a descriptive survey on the current status of nurses in advanced roles in the Western Pacific region, followed by a Delphi survey, and exploratory interviews. A total of 55 national experts with clinical, academic, and/or government-related backgrounds from 18 countries participated from December 2017 – December 2018. The descriptive survey via email to identify the status of nurses in advanced roles and a working definition was developed. This formed the basis for the Delphi survey, which identified key barriers and challenges for enhancing the development of nurses in advanced roles within the country (round 1) and for the region (rounds 2 and 3). Lastly, semi-structured individual interviews were conducted to identify strategies for establishing nurses in advanced roles to improve equitable access to healthcare.

Results

Thirty-seven roles and characteristics were identified and categorized for nurses performing advanced roles. Emergency care, critical care, elderly health, child health, and rural/remote communities were identified as fields with particular need for nurses in advanced roles in the Western Pacific region. Providing effective services, influencing government leadership, and advocating for health system sustainability were deemed necessary to improve equitable healthcare access. We found that nurses in advanced roles are not limited to clinical tasks within the hospital but are poised for active participation in primary healthcare, education/teaching, professional leadership, quality management, and research.

Conclusions

Demand for nurses in advanced roles is high in the Western Pacific region and 15 items were identified across five core strategic areas to enhance development of nurses in advanced roles. Governmental-level recommendations include establishing legislative protection, improving systems for remuneration, strengthening supportive channels, and conducting national needs assessments.
Trend and equity of general practitioners’ allocation in China based on the data from 2012–2017
Authors: Yu Qianqian , Yin Wenqiang , Huang Dongmei , Sun Kui , Chen Zhongming , Guo Hongwei , Wu Di
Published: February 2021

Background

General practitioners are the gatekeepers of the health of the residents. This study aims to evaluate the trend and equity of general practitioners' allocation from 2012 to 2017 in China and provide a reference for regional health planning and rational distribution of general practitioners.

Methods

We extracted the data of general practitioners from 22 provinces, 5 autonomous regions, and 4 municipalities of mainland China. The population and geographical area were taken from the China Statistical Yearbook. The general practitioners' data were taken from the China Health Statistical Yearbook. Lorenz curve, Gini coefficient, and agglomeration degree were used to analyze the data.

Results

The number of general practitioners was 252,717 in 2017, which equates to 1.82 per 10,000 residents, and accounts for 7.45% of the total number of practicing (assistant) doctors. From 2012 to 2017, the population-based Gini coefficient for general practitioners reduced from 0.31 to 0.24, while the geographical area-based Gini coefficient remained unchanged at 0.73. The agglomeration degree based on population increased from 0.72 to 0.73 in the western region including Tibet (0.403) and Shaanxi (0.513). Moreover, in the eastern region the agglomeration degree reduced from 1.477 to 1.329. In the middle region it rose from 0.646 to 0.802. The agglomeration degree based on the geographical area in the western region increased from 0.270 to 0.277 while the values in Tibet, Qinghai, Xinjiang were less than 0.1. In the eastern region, it reduced from 1.447 to 1.329. It increased from 1.149 to 1.423 in the middle region.

Conclusions

The number of general practitioners has increased significantly in China. It has a fair allocation based on population. However, the equity based on geographical area is low and uneven in different regions with large regional differences. In the western region, there is an allocation shortage with respect to population and geographical area. Concerned departments should establish and improve the incentive and performance appraisal mechanisms of general practitioners. The Internet + should be used to empower their service capacity and efficiency. The educational input should be increased for the western region and government should encourage the eastern region to support the western region.
Drug resistance and Cancer stem cells
Authors: Li Yuan , Wang Zhenning , Ajani Jaffer A. , Song Shumei
Published: February 2021

Therapy resistance is a major problem when treating cancer patients as cancer cells develop mechanisms that counteract the effect of therapeutic compounds, leading to fit and more aggressive clones that contribute to poor prognosis. Therapy resistance can be both intrinsic and/or acquired. These are multifactorial events, and some are related to factors including adaptations in cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), deregulation of key signaling pathways, drug efflux through ABC transporters, acquired mutations, evading apoptosis, and activation of DNA damage response among others. Among these factors, CSCs represent the major source of therapy resistance. CSCs are a subset of tumor cells that are capable of self-renewal and multilineage progenitor expansion that are known to be intrinsically resistant to anticancer treatments. Multiple clones of CSCs pre-exist, and some can adopt and expand easily to changes in the tumor microenvironment (TME) and/or in response to radio- and chemotherapy. A combination of both intrinsic and extrinsic factors contributes to CSC-mediated therapy resistance. In this review, we will focus on CSCs and therapy resistance as well as suggest strategies to eliminate CSCs and, therefore, overcome resistance.
Maternal feeding style and child weight status among Hispanic families with low-income levels: a longitudinal study of the direction of effects
Authors: Hughes Sheryl O. , Power Thomas G. , O’Connor Teresia M. , Fisher Jennifer O. , Micheli Nilda E. , Papaioannou Maria A.
Published: February 2021

Background

The home environment is a central and modifiable influence on the development of childhood obesity. Evidence supports the central role of parents in shaping problematic child eating behaviors and excess weight. Most studies of feeding emphasize parent-driven influences without taking into account the child’s role in eating interactions. Few studies have addressed the bi-directional nature of feeding dynamics in studies of young children.

Methods

The goals of this study were: 1) to examine if parental feeding styles during preschool (4–5 years) predict child weight status at 7–9 years, and 2) to examine the direction of effects between parental feeding styles and child weight status over time. Participants were part of a larger longitudinal study of Hispanic Head Start families living in the West South Central United States. Data from mother/child dyads were collected at three time points: Time 1 (ages 4–5), Time 2 (ages 5 ½-6 ½), and at Time 3 (ages 7–9). Only data from the Times 1 and 3 were used in the current analyses. A total of 128 mothers and their children had data on all variables needed for the analyses. Assessments included parent-reported feeding styles, feeding practices, acculturation, child eating behaviors, and child height and weight. Hierarchical regression was used to examine the first aim; a cross-lagged panel analysis examined the second aim.

Results

An indulgent parental feeding style at ages 4–5 was associated with increased child BMIz-score at ages 7–9. Indulgent feeding significantly contributed to child BMIz-score beyond demographics, baseline child BMIz-score, parental acculturation, and child eating behaviors. Regarding the direction of effects in parental feeding interactions, the cross-lagged analyses showed that both indulgent feeding style and authoritative feeding style at Time 1 positively predicted child BMIz-scores at Time 3. Child effects were significant as well. Child BMIz-score at Time 1 positively predicted indulgent feeding and negatively predicted authoritarian feeding at Time 3.

Conclusions

Indulgent feeding should be addressed in future family-focused childhood obesity initiatives focused on young children and their parents.
Exploring influences on evaluation practice: a case study of a national physical activity programme
Authors: Fynn Judith F. , Hardeman Wendy , Milton Karen , Jones Andy
Published: February 2021

Background

Interventions to improve physical activity behaviour are a core part of public health policy and practice. It is essential that we evaluate these interventions and use the evidence to inform decisions to improve population health. Evaluation of ‘real-world’ interventions provide an opportunity to generate practice-relevant evidence, however these interventions are difficult to evaluate. Various guidelines have been developed to facilitate evaluation, but evidence about their effectiveness in practice is limited. To explore influences on evaluation practice in an applied context, we conducted a case study of Sport England’s ‘Get Healthy Get Active’ (GHGA) programme. This was a national programme that funded 33 projects that were delivered and evaluated across England. The programme was chosen as it was designed to generate evidence on the role of sport in increasing physical activity and improving health. The study aimed to explore and appraise whether strategies intended to facilitate project evaluation, including funder requirements to use a standardised evaluation framework and specific data collection methods, were effective in generating evidence that enabled the programme to meet its aims.

Methods

We applied a collective case study design involving 35 semi-structured interviews, and documentary analysis of multiple sources of evidence from 23 physical activity projects funded by GHGA. We applied thematic and framework analysis. We developed a logic model and mapped actual outcomes against intended outcomes. A narrative synthesis is provided. We discuss implications for the effective commissioning and evaluation of public health interventions.

Results

We identified five main themes of influences on evaluation practices that can act as barriers and facilitators to good practice: programme and project design; evaluation design; partnerships; resources; and organisational structures and systems. These influences are context-specific and operate through a complex set of interactions.

Conclusion

Developing a better understanding of how influences on evaluation practice can act as facilitators or barriers is vital to help close current gaps in the evidence-based practice cycle. Critically, organisational structures and systems are needed to facilitate collaborative decision making; integration of projects and evaluation across partners organisations; transfer of knowldege and insights between stakeholders; and more rapid feedback and dissemination.
A theoretical model of health management using data-driven decision-making: the future of precision medicine and health
Authors: Kriegova Eva , Kudelka Milos , Radvansky Martin , Gallo Jiri
Published: February 2021

Background

The burden of chronic and societal diseases is affected by many risk factors that can change over time. The minimalisation of disease-associated risk factors may contribute to long-term health. Therefore, new data-driven health management should be used in clinical decision-making in order to minimise future individual risks of disease and adverse health effects.

Methods

We aimed to develop a health trajectories (HT) management methodology based on electronic health records (EHR) and analysing overlapping groups of patients who share a similar risk of developing a particular disease or experiencing specific adverse health effects. Formal concept analysis (FCA) was applied to identify and visualise overlapping patient groups, as well as for decision-making. To demonstrate its capabilities, the theoretical model presented uses genuine data from a local total knee arthroplasty (TKA) register (a total of 1885 patients) and shows the influence of step by step changes in five lifestyle factors (BMI, smoking, activity, sports and long-distance walking) on the risk of early reoperation after TKA.

Results

The theoretical model of HT management demonstrates the potential of using EHR data to make data-driven recommendations to support both patients’ and physicians’ decision-making. The model example developed from the TKA register acts as a clinical decision-making tool, built to show surgeons and patients the likelihood of early reoperation after TKA and how the likelihood changes when factors are modified. The presented data-driven tool suits an individualised approach to health management because it quantifies the impact of various combinations of factors on the early reoperation rate after TKA and shows alternative combinations of factors that may change the reoperation risk.

Conclusion

This theoretical model introduces future HT management as an understandable way of conceiving patients’ futures with a view to positively (or negatively) changing their behaviour. The model’s ability to influence beneficial health care decision-making to improve patient outcomes should be proved using various real-world data from EHR datasets.
Exercise rescues mitochondrial coupling in aged skeletal muscle: a comparison of different modalities in preventing sarcopenia
Authors: Harper Colin , Gopalan Venkatesh , Goh Jorming
Published: February 2021

Skeletal muscle aging is associated with a decline in motor function and loss of muscle mass- a condition known as sarcopenia. The underlying mechanisms that drive this pathology are associated with a failure in energy generation in skeletal muscle, either from age-related decline in mitochondrial function, or from disuse. To an extent, lifelong exercise is efficacious in preserving the energetic properties of skeletal muscle and thus may delay the onset of sarcopenia. This review discusses the cellular and molecular changes in skeletal muscle mitochondria during the aging process and how different exercise modalities work to reverse these changes. A key factor that will be described is the efficiency of mitochondrial coupling—ATP production relative to O2 uptake in myocytes and how that efficiency is a main driver for age-associated decline in skeletal muscle function. With that, we postulate the most effective exercise modality and protocol for reversing the molecular hallmarks of skeletal muscle aging and staving off sarcopenia. Two other concepts pertinent to mitochondrial efficiency in exercise-trained skeletal muscle will be integrated in this review, including- mitophagy, the removal of dysfunctional mitochondrial via autophagy, as well as the implications of muscle fiber type changes with sarcopenia on mitochondrial function.
Retraction Note to: Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade
Authors: Kuo Hsing-Chun , Lu Chien-Chang , Shen Chien-Heng , Tung Shui-Yi , Hsieh Meng Chiao , Lee Ko-Chao , Lee Li-Ya , Chen Chin-Chu , Teng Chih-Chuan , Huang Wen-Shih , Chen Te-Chuan , Lee Kam-Fai
Published: February 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12967-016-0831-y.
Ceria nanoparticles ameliorate white matter injury after intracerebral hemorrhage: microglia-astrocyte involvement in remyelination
Authors: Zheng Jingwei , Lu Jia’nan , Mei Shuhao , Wu Haijian , Sun Zeyu , Fang Yuanjian , Xu Shenbin , Wang Xiaoyu , Shi Ligen , Xu Weilin , Chen Sheng , Yu Jun , Liang Feng , Zhang Jianmin
Published: February 2021

Background

Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration.

Methods

ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms.

Results

CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia.

Conclusion

The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.
Peripheral electrical stimulation to reduce pathological tremor: a review
Authors: Pascual-Valdunciel Alejandro , Hoo Grace W. , Avrillon Simon , Barroso Filipe Oliveira , Goldman Jennifer G. , Hernandez-Pavon Julio C. , Pons José L.
Published: February 2021

Interventions to reduce tremor in essential tremor (ET) and Parkinson’s disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.
Learning regularized representations of categorically labelled surface EMG enables simultaneous and proportional myoelectric control
Authors: Olsson Alexander E. , Malešević Nebojša , Björkman Anders , Antfolk Christian
Published: February 2021

Background

Processing the surface electromyogram (sEMG) to decode movement intent is a promising approach for natural control of upper extremity prostheses. To this end, this paper introduces and evaluates a new framework which allows for simultaneous and proportional myoelectric control over multiple degrees of freedom (DoFs) in real-time. The framework uses multitask neural networks and domain-informed regularization in order to automatically find nonlinear mappings from the forearm sEMG envelope to multivariate and continuous encodings of concurrent hand- and wrist kinematics, despite only requiring categorical movement instruction stimuli signals for calibration.

Methods

Forearm sEMG with 8 channels was collected from healthy human subjects (N = 20) and used to calibrate two myoelectric control interfaces, each with two output DoFs. The interfaces were built from (I) the proposed framework, termed Myoelectric Representation Learning (MRL), and, to allow for comparisons, from (II) a standard pattern recognition framework based on Linear Discriminant Analysis (LDA). The online performances of both interfaces were assessed with a Fitts’s law type test generating 5 quantitative performance metrics. The temporal stabilities of the interfaces were evaluated by conducting identical tests without recalibration 7 days after the initial experiment session.

Results

Metric-wise two-way repeated measures ANOVA with factors method (MRL vs LDA) and session (day 1 vs day 7) revealed a significant ($$p<0.05$$

p
<
0.05

) advantage for MRL over LDA in 5 out of 5 performance metrics, with metric-wise effect sizes (Cohen’s $$d$$
d
) separating MRL from LDA ranging from $$\left|d\right|=0.62$$

d

=
0.62

to $$\left|d\right|=1.13$$

d

=
1.13

. No significant effect on any metric was detected for neither session nor interaction between method and session, indicating that none of the methods deteriorated significantly in control efficacy during one week of intermission.

Conclusions

The results suggest that MRL is able to successfully generate stable mappings from EMG to kinematics, thereby enabling myoelectric control with real-time performance superior to that of the current commercial standard for pattern recognition (as represented by LDA). It is thus postulated that the presented MRL approach can be of practical utility for muscle-computer interfaces.
Systematic review of gut microbiota and attention-deficit hyperactivity disorder (ADHD)
Authors: Sukmajaya Alverina Cynthia , Lusida Maria Inge , Soetjipto  , Setiawati Yunias
Published: February 2021

Background

Gut–brain axis (GBA) is a system widely studied nowadays, especially in the neuropsychiatry field. It is postulated to correlate with many psychiatric conditions, one of them being attention-deficit hyperactivity disorder (ADHD). ADHD is a disorder that affects many aspects of life, including but not limited to financial, psychosocial, and cultural aspects. Multiple studies have made a comparison of the gut microbiota between ADHD and healthy controls. Our aims were to review the existing studies analyzing the gut microbiota between human samples in ADHD and healthy individuals.

Methods

The literature was obtained using Google Scholar, Pubmed, and Science Direct search engine. The keywords used were “ADHD”, “gut microbiota”, “stool”, “gut”, and “microbiota”. The selected studies were all case–control studies, which identify the gut microbiota between ADHD and healthy individuals.

Result

We found six studies which were eligible for review. The model and methods of each study is different. Forty-nine bacterial taxa were found, yet none of them can explain the precise relationship between ADHD and the gut microbiota. Bifidobacterium was found in higher amount in ADHD patients, but other study stated that the abundance of this genus was lower in ADHD with post-micronutrient treatment. This may suggest that micronutrient can modulate the population of Bifidobacterium and improve the behavior of ADHD patients. Other notable findings include a significantly lower population of Dialister in unmedicated ADHD, which rose after patients were medicated. A smaller amount of Faecalibacterium were also found in ADHD patients. This may explain the pathogenesis of ADHD, as Faecalibacterium is known for its anti-inflammatory products. It is possible the scarcity of this genera could induce overproduction of pro-inflammatory cytokines, which is in accordance with the high level of pro-inflammatory cytokines found in children with ADHD.

Conclusion

There were no studies that examined which bacterial taxa correlated most to ADHD. This might occur due to the different model and methods in each study. Further study is needed to identify the correlation between gut microbiota and ADHD.
Finite element analysis of wedge and biconcave deformity in four different height restoration after augmentation of osteoporotic vertebral compression fractures
Authors: Zuo Xiao-Hua , Chen Yin-Bing , Xie Peng , Zhang Wen-Dong , Xue Xiang-Yun , Zhang Qian-Xi , Shan Ben , Zhang Xiao-Bing , Bao Hong-Guang , Si Yan-Na
Published: February 2021

Purpose

Biomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA).

Methods

Three-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0–3 grade) after T12 vertebral augmentation.

Results

In wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture.

Conclusions

The vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.
Remodeling Alzheimer-amyloidosis models by seeding
Authors: Ulm Brittany S. , Borchelt David R. , Moore Brenda D.
Published: February 2021

Alzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.
Novel hybrid polyester-polyacrylate hydrogels enriched with platelet-derived growth factor for chondrogenic differentiation of adipose-derived mesenchymal stem cells in vitro
Authors: Valipour Fereshteh , Valipour Farzaneh , Rahbarghazi Reza , Navali Amir Mohammad , Rashidi Mohammad Reza , Davaran Soodabeh
Published: February 2021

Background

The goal of the present study was to create a new biodegradable hybrid PCL-P (HEMA-NIPAAm) thermosensitive hydrogel scaffold by grafting PNIPAAm-based copolymers with biodegradable polyesters to promote the chondrogenic differentiation of human progenitor cells (adipose-derived stem cells-hASCs) in the presence of the platelet-derived growth factor (PDGF-BB). Different mixture ratios including 50 mmol ε-caprolactone and 10 mmol HEMA (S-1), 30 mmol ε-caprolactone and 10 mmol HEMA (S-2), 10 mmol ε-caprolactone and 30 mmol HEMA (S-3) were copolymerized followed by the addition of NIPAAm.

Results

A mild to moderate swelling and wettability rates were found in S-2 group copmpared to the S-1 ans S-3 samples. After 7 weeks, S-2 degradation rate reached ~ 43.78%. According to the LCST values, S-2, reaching 37 °C, was selected for different in vitro assays. SEM imaging showed nanoparticulate structure of the scaffold with particle size dimensions of about 62–85 nm. Compressive strength, Young’s modulus, and compressive strain (%) of S-2 were 44.8 MPa, 0.7 MPa, and 75.5%. An evaluation of total proteins showed that the scaffold had the potential to gradually release PDGF-BB. When hASCs were cultured on PCL-P (HEMA-NIPAAm) in the presence of PDGF-BB, the cells effectively attached and flattened on the scaffold surface for a period of at least 14 days, the longest time point evaluated, with increased cell viability rates as measured by performing an MTT assay (p < 0.05). Finally, a real-time RT-PCR analysis demonstrated that the combination of PCL-P (HEMA-NIPAAm) and PDGF-BB promoted the chondrogenesis of hASCs over a period of 14 days by up-regulating the expression of aggrecan, type-II collagen, SOX9, and integrin β1 compared with the non-treated control group (p < 0.05).

Conclusion

These results demonstrate that the PCL-P(HEMA-NIPAAm) hydrogel scaffold carrying PDGF-BB as a matrix for hASC cell seeding is a valuable system that may be used in the future as a three-dimensional construct for implantation in cartilage injuries.