bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymptomatic and submicroscopic Plasmodium infections in an area before and during integrated vector control in Homa Bay, western Kenya
Authors: Omondi Collince J. , Otambo Wilfred O. , Odongo David , Ochwedo Kevin O. , Otieno Antony , Onyango Shirley A. , Orondo Pauline , Ondeto Benyl M. , Lee Ming-Chieh , Zhong Daibin , Kazura James W. , Githeko Andrew K. , Yan Guiyun 
Published: September 2022

Abstract
Background
Long-lasting insecticidal nets (LLINs) have been the primary vector control strategy until indoor residual spraying (IRS) was added in Homa Bay and Migori Counties in western Kenya. The objective of this study was to evaluate the impact of LLINs integrated with IRS on the prevalence of asymptomatic and submicroscopic Plasmodium infections in Homa Bay County.

Methods
A two-stage cluster sampling procedure was employed to enroll study participants aged ≥ 6 months old. Four consecutive community cross-sectional surveys for Plasmodium infection were conducted in residents of Homa Bay county, Kenya. Prior to the start of the study, all study households received LLINs, which were distributed between June 2017 and March 2018. The first (February 2018) and second (June 2018) surveys were conducted before and after the first round of IRS (Feb–Mar 2018), while the third (February 2019) and fourth (June 2019) surveys were conducted before and after the second application of IRS (February–March 2019). Finger-prick blood samples were obtained to prepare thick and thin smears for microscopic determination and qPCR diagnosis of Plasmodium genus.

Results
Plasmodium spp. infection prevalence by microscopy was 18.5% (113/610) before IRS, 14.2% (105/737) and 3.3% (24/720) after the first round of IRS and 1.3% (11/849) after the second round of IRS (p < 0.0001). Submicroscopic (blood smear negative, qPCR positive) parasitaemia reduced from 18.9% (115/610) before IRS to 5.4% (46/849) after IRS (p < 0.0001). However, the proportion of PCR positive infections that were submicroscopic increased from 50.4% (115/228) to 80.7% (46/57) over the study period (p < 0.0001). Similarly, while the absolute number and proportions of microscopy positives which were asymptomatic decreased from 12% (73/610) to 1.2% (9/849) (p < 0.0001), the relative proportion increased. Geometric mean density of P. falciparum parasitaemia decreased over the 2-year study period (p < 0.0001).

Conclusions
These data suggest that two annual rounds of IRS integrated with LLINs significantly reduced the prevalence of Plasmodium parasitaemia, while the proportion of asymptomatic and submicroscopic infections increased. To reduce cryptic P. falciparum transmission and improve malaria control, strategies aimed at reducing the number of asymptomatic and submicroscopic infections should be considered.
Essential phospholipids decrease apoptosis and increase membrane transport in human hepatocyte cell lines
Authors: Wupperfeld Dominik , Fricker Gert , Bois De Fer Béatrice , Frank Larissa , Wehrle Annika , Popovic Branko 
Published: September 2022

Abstract
Background
Essential phospholipids (EPL) have hepatoprotective effects across many liver diseases/conditions. The impact of EPL on hepatocyte function in vitro was investigated.

Methods
Effects of noncytotoxic concentrations of EPL (0.1 and 0.25 mg/ml), and its constituents, polyenylphosphatidylcholine (PPC) and phosphatidylinositol (PI) (both at 0.1 and 1 mg/ml), on membrane fluidity, apoptosis and extracellular transport versus controls were investigated in human hepatocyte cell lines (HepG2, HepaRG, steatotic HepaRG).

Results
Significantly increased membrane fluidity occurred with all 3 phospholipids (PLs) in HepG2 cultures, and with PI (1 mg/ml) in steatotic HepaRG cells. Significantly decreased tamoxifen-induced apoptosis was observed in HepG2 cells with EPL, PPC and PI. Breast cancer resistance protein (BCRP) activity was significantly increased by EPL and PI in HepG2 cells. Multidrug resistance-associated protein 2 (MRP-2) activity was unaffected by any PL in HepG2 cells, and significantly increased by EPL, PI and PPC (1 mg/ml) in HepaRG cells, and by PI (1 mg/ml) in steatotic HepaRG cells. Bile salt export protein (BSEP) activity in HepG2 cells and steatotic HepaRG cells was significantly increased by EPL (0.25 mg/ml), and PPC (both concentrations), but not by PI. The PLs had no effects on HepaRG cell BSEP activity. P-glycoprotein (P-GP) activity was significantly increased by all compounds in HepG2 cells. PI (1 mg/ml) significantly increased P-GP activity in HepaRG and steatotic HepaRG cells.

Conclusions
EPL, PPC, and PI increased hepatocyte membrane fluidity, decreased apoptosis and increased hepatocellular export, all of which may improve liver function. These in-vitro investigations provide valuable insights into the mechanism of action of EPL.
Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer
Authors: Yadav Priya , Ambudkar Suresh V. , Rajendra Prasad N. 
Published: September 2022

AbstractCancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core–shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers.
Graphical Abstract
Small extracellular vesicles of hypoxic endothelial cells regulate the therapeutic potential of adipose-derived mesenchymal stem cells via miR-486-5p/PTEN in a limb ischemia model
Authors: Shen Zekun , Wang Weiyi , Chen Jinxing , Chen Bingyi , Tang Yanan , Hou Jiaxuan , Li Jiayan , Liu Shuang , Mei Yifan , Zhang Liwei , Lu Shaoying 
Published: September 2022

Abstract
Background
Patients with critical limb ischemia (CLI) are at great risk of major amputation and cardiovascular events. Adipose-derived mesenchymal stem cell (ADSC) therapy is a promising therapeutic strategy for CLI, but the poor engraftment and insufficient angiogenic ability of ADSCs limit their regenerative potential. Herein, we explored the potential of human umbilical vein endothelial cells (HUVECs)-derived small extracellular vesicles (sEVs) for enhancing the therapeutic efficacy of ADSCs in CLI.

Results
sEVs derived from hypoxic HUVECs enhanced the resistance of ADSCs to reactive oxygen species (ROS) and further improved the proangiogenic ability of ADSCs in vitro. We found that the hypoxic environment altered the composition of sEVs from HUVECs and that hypoxia increased the level of miR-486-5p in sEVs. Compared to normoxic sEVs (nsEVs), hypoxic sEVs (hsEVs) of HUVECs significantly downregulated the phosphatase and tensin homolog (PTEN) via direct targeting of miR-486-5p, therefore activating the AKT/MTOR/HIF-1α pathway and influencing the survival and pro-angiogenesis ability of ADSCs. In a hindlimb ischemia model, we discovered that hsEVs-primed ADSCs exhibited superior cell engraftment, and resulted in better angiogenesis and tissue repair.

Conclusion
hsEVs could be used as a therapeutic booster to improve the curative potential of ADSCs in a limb ischemia model. This finding offers new insight for CLI treatment.

Graphical Abstract
Perceptions of gender equity and markers of achievement in a National Institute for Health Research Biomedical Research Centre: a qualitative study
Authors: Henderson Lorna R. , Dam Rinita , Shah Syed Ghulam Sarwar , Ovseiko Pavel V. , Kiparoglou Vasiliki 
Published: September 2022

Abstract
Background
The need to improve gender equity (GE) in academic medicine is well documented. Biomedical Research Centres (BRCs), partnerships between leading National Health Service (NHS) organizations and universities in England, conduct world-class translational research funded by the National Institute for Health and Care Research (NIHR). In 2011, eligibility for BRC funding was restricted to universities demonstrating sustained GE success recognized by the Athena SWAN Charter for Women in Science Silver awards. Despite this structural change, GE research in BRC settings is underdeveloped, yet critical to the acceleration of women’s advancement and leadership. To explore both women’s and men’s perceptions of GE and current markers of achievement in a BRC setting.

Methods
Thematic analysis of data from two research projects: 53 GE survey respondents’ free-text comments (34 women, 16 men), and 16 semi-structured interviews with women affiliated to the NIHR Oxford BRC.

Results
Four major themes emerged from the analysis: perceptions of the Athena SWAN Charter for Women in Science (GE policy); views on monitoring GE in BRCs; views on current markers of achievement in academia and GE; and recommendations for actions to improve GE in BRC settings. Monitoring of GE in BRCs was deemed to be important, but complex. Participants felt that current markers of achievement were not equitable to women, as they did not take contextual factors into account such as maternity leave and caring responsibilities. BRC-specific organizational policies and metrics are needed in order to monitor and catalyse GE.

Conclusions
Markers of achievement for monitoring GE in BRCs should consider contextual factors specific to BRCs and women’s career progression and professional advancement. GE markers of achievement should be complemented with broader aspects of equality, diversity and inclusion.
Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3
Authors: Shen Tianyi , Miao Suqin , Zhou Yulin , Yi Xiaoming , Xue Song , Du Bowen , Tang Chaopeng , Qu Le , Fu Dian , Jia Ruipeng , He Haowei 
Published: September 2022

Abstract
Background
Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear.

Methods
Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation.

Results
The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-β and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo.

Conclusion
Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC.
The neighbourhood built environment and health-related fitness: a narrative systematic review
Authors: Frehlich Levi , Christie Chelsea D. , Ronksley Paul E. , Turin Tanvir C. , Doyle-Baker Patricia , McCormack Gavin R. 
Published: September 2022

AbstractBackgroundThere is increasing evidence demonstrating the importance of the neighbourhood built environment in supporting physical activity. Physical activity provides numerous health benefits including improvements in health-related fitness (i.e., muscular, cardiorespiratory, motor, and morphological fitness). Emerging evidence also suggests that the neighbourhood built environment is associated with health-related fitness. Our aim was to summarize evidence on the associations between the neighbourhood built environment and components of health-related fitness in adults.MethodsWe undertook a systematic review following PRISMA guidelines. Our data sources included electronic searches in MEDLINE, Embase, CINAHL, Web of Science, SPORTDiscus, Environment Complete, ProQuest Dissertations and Theses, and Transport Research International Documentation from inception to March 2021. Our eligibility criteria consisted of observational and experimental studies estimating associations between the neighbourhood built environment and health-related fitness among healthy adults (age ≥ 18 years). Eligible studies included objective or self-reported measures of the neighbourhood built environment and included either objective or self-reported measures of health-related fitness. Data extraction included study design, sample characteristics, measured neighbourhood built environment characteristics, and measured components of health-related fitness. We used individual Joanna Briggs Institute study checklists based on identified study designs. Our primary outcome measure was components of health-related fitness (muscular; cardiorespiratory; motor, and morphological fitness).ResultsTwenty-seven studies (sample sizes = 28 to 419,562; 2002 to 2020) met the eligibility criteria. Neighbourhood destinations were the most consistent built environment correlate across all components of health-related fitness. The greatest number of significant associations was found between the neighbourhood built environment and morphological fitness while the lowest number of associations was found for motor fitness. The neighbourhood built environment was consistently associated with health-related fitness in studies that adjusted for physical activity.ConclusionThe neighbourhood built environment is associated with health-related fitness in adults and these associations may be independent of physical activity. Longitudinal studies that adjust for physical activity (including resistance training) and sedentary behaviour, and residential self-selection are needed to obtain rigorous causal evidence for the link between the neighbourhood built environment and health-related fitness.Trial registrationProtocol registration: PROSPERO number CRD42020179807.
An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas
Authors: Ahmadi-Beni Reza , Shahbazi Shirin , Khoshnevisan Alireza 
Published: September 2022

Abstract
Background
Lack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differentially expressed genes is one of the core approaches to clarify the causative factors.

Methods
Microarray datasets of the treatment-naïve gliomas were provided from the Gene Expression Omnibus considering the similar platform and batch effect removal. Interacting recovery of the top differentially expressed genes was performed on the STRING and Cytoscape platforms. Kaplan–Meier analysis was piloted using RNA sequencing data and the survival rate of glioma patients was checked considering selected genes. To validate the bioinformatics results, the gene expression was elucidated by real-time RT-qPCR in a series of low and high-grade fresh tumor samples.

Results
We identified 323 up-regulated and 253 down-regulated genes. The top 20 network analysis indicated that PTX3, TIMP1, CHI3L1, LTF and IGFBP3 comprise a crucial role in gliomas progression. The survival was inversely linked to the levels of all selected genes. Further analysis of RNA sequencing data indicated a significant increase in all five genes in high-grade tumors. Among them, PTX3, TIMP1 and LTF did not show any change in low-grade versus controls. Real-time RT-qPCR confirmed the in-silico results and revealed significantly higher expression of selected genes in high-grade samples compared to low-grade.

Conclusions
Our results highlighted the role of PTX3 and TIMP1 which were previously considered in glioma tumorigenesis as well as LTF as a new potential biomarker.
Traditional Khmer Medicine and its role in wildlife use in modern-day Cambodia
Authors: Lim Thona , Davis Elizabeth Oneita , Crudge Brian , Roth Vichet , Glikman Jenny Anne 
Published: September 2022

AbstractIndividuals across Cambodia depend on the use of natural products in Traditional Khmer Medicine (TKM), a traditional medicine system in Cambodia that has been practiced for hundreds of years. Cambodia is rich in fauna and flora species, many of which have been, and continue to be, traded domestically for traditional medicine use. Combined with other known exploitative practices, such as snaring for wild meat consumption and international trade in wildlife, domestic trade in wildlife medicine threatens populations of regional conservation importance. Here, we provide an updated understanding about how TKM is practiced in modern times; how TKM practices are transmitted and adapted; and roles of wildlife part remedies in TKM historically and presently. We conducted semi-structured interviews with TKM practitioners in Stung Treng, Mondulkiri Province, and at the National Center for Traditional Medicine in Phnom Penh, the capital of Cambodia. TKM is generally practiced in the private sector and is mostly informal, without enrollment in any academic training. TKM practitioner roles commonly involve collecting, preparing, selling, and advising on medicine, rather than providing direct treatment. Over half of the interviewed TKM practitioners (57.6%) were still prescribing wildlife parts as medicine over the past 5 years, with 28 species of wild animals reported. Lorises and porcupine were the wildlife products cited as being in highest demand in TKM, primarily prescribed for women’s illnesses such as post-partum fatigue (Toas and Sawsaye kchey). However, the supply of wildlife products sourced from the wild was reported to have dropped in the 5 years prior to the survey, which represents an opportunity to reduce prescription of threatened wildlife. We suggest that our results be used to inform tailored demand reduction interventions designed to encourage greater reliance on biomedicine and non-threatened plants, particularly in rural areas where use of biomedicine may still be limited.
A citation analysis and scoping systematic review of the operationalization of the Practical, Robust Implementation and Sustainability Model (PRISM)
Authors: Rabin Borsika A. , Cakici Julie , Golden Caitlin A. , Estabrooks Paul A. , Glasgow Russell E. , Gaglio Bridget 
Published: September 2022

Abstract
Background
The Practical, Robust Implementation and Sustainability Model (PRISM) was developed in 2008 as a contextually expanded version of the broadly used Reach, Adoption, Effectiveness, Implementation, and Maintenance (RE-AIM) framework. PRISM provides researchers a pragmatic and intuitive model to improve translation of research interventions into clinical and community practice. Since 2008, the use of PRISM increased across diverse topics, populations, and settings. This citation analysis and scoping systematic review aimed to assess the use of the PRISM framework and to make recommendations for future research.

Methods
A literature search was conducted using three databases (PubMed, Web of Science, Scopus) for the period of 2008 and September 2020. After exclusion, reverse citation searches and invitations to experts in the field were used to identify and obtain recommendations for additional articles not identified in the original search. Studies that integrated PRISM into their study design were selected for full abstraction. Unique research studies were abstracted for information on study characteristics (e.g., setting/population, design), PRISM contextual domains, and RE-AIM outcomes.

Results
A total of 180 articles were identified to include PRISM to some degree. Thirty-two articles representing 23 unique studies integrated PRISM within their study design. Study characteristics varied widely and included studies conducted in diverse contexts, but predominately in high-income countries and in clinical out-patient settings. With regards to use, 19 used PRISM for evaluation, 10 for planning/development, 10 for implementation, four for sustainment, and one for dissemination. There was substantial variation across studies in how and to what degree PRISM contextual domains and RE-AIM outcomes were operationalized and connected. Only two studies directly connected individual PRISM context domains with RE-AIM outcomes, and another four included RE-AIM outcomes without direct connection to PRISM domains.

Conclusions
This is the first systematic review of the use of PRISM in various contexts. While there were low levels of ‘integrated’ use of PRISM and few reports on linkage to RE-AIM outcomes, most studies included important context domains of implementation and sustainability infrastructure and external environment. Recommendations are provided for more consistent and comprehensive use of and reporting on PRISM to inform both research and practice on contextual factors in implementation.