bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation barriers and remedial strategies for community-based health insurance in Bangladesh: insights from national stakeholders
Authors: Sheikh Nurnabi , Tagoe Eunice Twumwaa , Akram Raisul , Ali Nausad , Howick Susan , Morton Alec
Published: September 2022

Background

Community-based health insurance (CBHI) is a part of the health system in Bangladesh, and overcoming the obstacles of CBHI is a significant policy concern that has received little attention. The purpose of this study is to analyze the implementation barriers of voluntary CBHI schemes in Bangladesh and the strategies to overcome these barriers from the perspective of national stakeholders.

Methods

This study is exploratory qualitative research, specifically case study design, using key informant interviews to investigate the barriers of CBHI that are faced during the implementation. Using a topic guide, we conducted thirteen semi-structured in-depth interviews with key stakeholders directly involved in the CBHI implementation process. The data were analyzed using the Framework analysis method.

Results

The implementation of CBHI schemes in Bangladesh is being constrained by several issues, including inadequate population coverage, adverse selection and moral hazard, lack of knowledge about health insurance principles, a lack of external assistance, and insufficient medical supplies. Door-to-door visits by local community-health workers, as well as regular promotional and educational campaigns involving community influencers, were suggested by stakeholders as ways to educate and encourage people to join the schemes. Stakeholders emphasized the necessity of external assistance and the design of a comprehensive benefits package to attract more people. They also recommended adopting a public–private partnership with a belief that collaboration among the government, microfinance institutions, and cooperative societies will enhance trust and population coverage in Bangladesh.

Conclusions

Our research concludes that systematically addressing implementation barriers by including key stakeholders would be a significant reform to the CBHI model, and could serve as a foundation for the planned national health protection scheme for Bangladesh leading to universal health coverage.
Improved biomarker discovery through a plot twist in transcriptomic data analysis
Authors: Sánchez-Baizán Núria , Ribas Laia , Piferrer Francesc
Published: September 2022

Background

Transcriptomic analysis is crucial for understanding the functional elements of the genome, with the classic method consisting of screening transcriptomics datasets for differentially expressed genes (DEGs). Additionally, since 2005, weighted gene co-expression network analysis (WGCNA) has emerged as a powerful method to explore relationships between genes. However, an approach combining both methods, i.e., filtering the transcriptome dataset by DEGs or other criteria, followed by WGCNA (DEGs + WGCNA), has become common. This is of concern because such approach can affect the resulting underlying architecture of the network under analysis and lead to wrong conclusions. Here, we explore a plot twist to transcriptome data analysis: applying WGCNA to exploit entire datasets without affecting the topology of the network, followed with the strength and relative simplicity of DEG analysis (WGCNA + DEGs). We tested WGCNA + DEGs against DEGs + WGCNA to publicly available transcriptomics data in one of the most transcriptomically complex tissues and delicate processes: vertebrate gonads undergoing sex differentiation. We further validate the general applicability of our approach through analysis of datasets from three distinct model systems: European sea bass, mouse, and human.

Results

In all cases, WGCNA + DEGs clearly outperformed DEGs + WGCNA. First, the network model fit and node connectivity measures and other network statistics improved. The gene lists filtered by each method were different, the number of modules associated with the trait of interest and key genes retained increased, and GO terms of biological processes provided a more nuanced representation of the biological question under consideration. Lastly, WGCNA + DEGs facilitated biomarker discovery.

Conclusions

We propose that building a co-expression network from an entire dataset, and only thereafter filtering by DEGs, should be the method to use in transcriptomic studies, regardless of biological system, species, or question being considered.
Berberine supplementation modulates the somatotropic axis and ameliorates glucose tolerance in dairy goats during late gestation and early lactation
Authors: Ghavipanje Navid , Fathi Nasri Mohammad Hasan , Farhangfar Seyyed Homayoun , Ghiasi Seyyed Ehsan , Vargas-Bello-Pérez Einar
Published: September 2022

Background

Pregnancy, parturition, and the onset of lactation represent an enormous physiological and hormonal challenge to the homeostasis of dairy animals, being a risk for their health and reproduction. Thus, as a part of the homothetic changes in preparturition period, goats undergo a period of IR as well as uncoupled GH/IGF-1 axis. The objective for this study was to determine the effect of berberine (BBR) during the peripartal period on hormonal alteration and somatotropic axis in dairy goats as well as glucose and insulin kinetics during an intravenous glucose tolerance test (IVGTT). At 21 days before the expected kidding date, 24 primiparous Saanen goats were assigned randomly to 4 dietary treatments. Goats were fed a basal diet from wk. 3 antepartum (AP) until wk. 3 postpartum (PP) supplemented with 0 (CTRL), 1 (BBR1), 2 (BBR2), and 4 (BBR4) g/d BBR. Blood samples were collected on days − 21, − 14, − 7, 0, 7, 14, and 21 relative to the expected kidding date. An IVGTT was also performed on day 22 PP.

Results

Compared with CTRL, supplementation with either BBR2 or BBR4 increased DMI at kidding day and PP, as well as body conditional score (BCS) and milk production (p ≤ 0.05). On d 7 and 14 PP plasma glucose was higher in BBR2- and BBR4-treated than in CTRL. The glucagon concentration was not affected by BBR during the experimental period. However, supplemental BBR indicated a tendency to decrease in cortisol concentration on days 7 (p = 0.093) and 14 (p = 0.100) PP. Lower plasma GH was observed in BBR than in non-BBR goats (p ≤ 0.05). Plasma IGF-1 concentration was enhanced in both BBR2 and BBR4 at kidding and day 7 PP (p ≤ 0.05). During the IVGTT, glucose area under the curve (AUC), clearance rate (CR), T1/2, and Tbasal was lower (p ≤ 0.05) in both BBR2 and BBR4 goats as compared with CTRL. Likewise, the insulin CR was higher (p ≤ 0.05) in goats receiving either BBR2 or BBR4 which was accompanied by a lower insulin T1/2 and AUC.

Conclusions

Altogether, our results indicated an improved glucose and insulin status along with the modulation of the somatotropic axis and glucose and insulin response to IVGTT in dairy goats supplemented with 2 and 4 g/d BBR.
Metabolic engineering of Escherichia coli for efficient production of L-5-hydroxytryptophan from glucose
Authors: Zhang Zhen , Yu Zichen , Wang Jinduo , Yu Yifa , Li Lanxiao , Sun Pengjie , Fan Xiaoguang , Xu Qingyang
Published: September 2022

Background

5-hydroxytryptophan (5-HTP), the direct biosynthetic precursor of the neurotransmitter 5-hydroxytryptamine, has been shown to have unique efficacy in the treatment of a variety of disorders, including depression, insomnia, and chronic headaches, and is one of the most commercially valuable amino acid derivatives. However, microbial fermentation for 5-HTP production continues to face many challenges, including low titer/yield and the presence of the intermediate L-tryptophan (L-Trp), owing to the complexity and low activity of heterologous expression in prokaryotes. Therefore, there is a need to construct an efficient microbial cell factory for 5-HTP production.

Results

We describe the systematic modular engineering of wild-type Escherichia coli for the efficient fermentation of 5-HTP from glucose. First, a xylose-induced T7 RNA polymerase-PT7 promoter system was constructed to ensure the efficient expression of each key heterologous pathway in E. coli. Next, a new tryptophan hydroxylase mutant was used to construct an efficient tryptophan hydroxylation module, and the cofactor tetrahydrobiopterin synthesis and regeneration pathway was expressed in combination. The L-Trp synthesis module was constructed by modifying the key metabolic nodes of tryptophan biosynthesis, and the heterologous synthesis of 5-HTP was achieved. Finally, the NAD(P)H regeneration module was constructed by the moderate expression of the heterologous GDHesi pathway, which successfully reduced the surplus of the intermediate L-Trp. The final engineered strain HTP11 was able to produce 8.58 g/L 5-HTP in a 5-L bioreactor with a yield of 0.095 g/g glucose and a maximum real-time productivity of 0.48 g/L/h, the highest values reported by microbial fermentation.

Conclusion

In this study, we demonstrate the successful design of a cell factory for high-level 5-HTP production, combined with simple processes that have potential for use in industrial applications in the future. Thus, this study provides a reference for the production of high-value amino acid derivatives using a systematic modular engineering strategy and a basis for an efficient engineered strain development of 5-HTP high-value derivatives.
Multifaceted characterization of the biological and transcriptomic signatures of natural killer cells derived from cord blood and placental blood
Authors: Gao Haibo , Liu Min , Zhang Yawei , Zhang Leisheng , Xie Baoguo
Published: September 2022

Background

Perinatal blood including umbilical cord blood and placental blood are splendid sources for allogeneic NK cell generation with high cytotoxicity of combating pathogenic microorganism and malignant tumor. Despite the generation of NK cells from the aforementioned perinatal blood, yet the systematical and detailed information of the biological and transcriptomic signatures of UC-NKs and P-NKs before large-scale clinical applications in disease remodeling is still largely obscure.

Methods

Herein, we took advantage of the “3IL”-based strategy for high-efficient generation of NK cells from umbilical cord blood and placental blood (UC-NKs and P-NKs), respectively. On the one hand, we conducted flow cytometry (FCM) assay and coculture to evaluate the subpopulations, cellular vitality and cytotoxic activity of the aforementioned NK cells. On the other hand, with the aid of RNA-SEQ and multiple bioinformatics analyses, we further dissected the potential diversities of UC-NKs and P-NKs from the perspectives of transcriptomes.

Results

On the basis of the “3IL” strategy, high-efficient NKs were generated from mononuclear cells (MNCs) in perinatal blood. P-NKs revealed comparable ex vivo expansion but preferable activation and cytotoxicity upon K562 cells over UC-NKs. Both of the two NKs showed diversity in cellular vitality and transcriptome including apoptotic cells, cell cycle, gene expression profiling and the accompanied multifaceted biological processes.

Conclusions

Our data revealed the multifaceted similarities and differences of UC-NKs and P-NKs both at the cellular and molecular levels. Our findings supply new references for allogeneic NK cell-based immunotherapy in regenerative medicine and will benefit the further exploration for illuminating the underlying mechanism as well.
Identification and validation of a ferroptosis-related gene to predict survival outcomes and the immune microenvironment in lung adenocarcinoma
Authors: Deng Biao , Xiang Jing , Liang Zhu , Luo Lianxiang
Published: September 2022

Background

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death worldwide. Ferroptosis, a form of cell death characterized by iron-dependent lipid peroxidation. However, the involvement of ferroptosis in the regulation of immune cell infiltration and its immunotherapeutic efficacy in LUAD remain unclear.

Methods

The Cancer Genome Atlas (TCGA) LUAD cohort was used to assess the survival prognosis of FRGs and construct a seven-gene risk signature. Correlation tests, difference tests, and a cluster analysis were performed to explore the role of FRGs in the immune microenvironment and their immunotherapeutic efficacy in LUAD. The effects of FRGs on LUAD cells were assessed by Western blot, iron assay, and lipid peroxidation assay.

Results

The seven-gene risk signatures of patients with LUAD were established and validated. FRG clustering based on 70 differentially expressed FRGs was associated with the immune microenvironment and indicated potential immune subtypes of LUAD. The seven-gene risk signature was an independent prognostic factor for LUAD and was used to divide the LUAD cohort into a high-risk and a low-risk group. Immunocyte infiltration levels, immune checkpoints, and immunotherapy response rates were significantly different between the two groups. Patients with high risk scores had lower overall levels of immunocyte infiltration but higher immunotherapy response rates. The key gene ribonucleotide reductase subunit M2 (RRM2) was associated with LUAD prognosis, which may be related to its ability to regulate the infiltration levels of activated mast cells and activated CD4 memory T cells. In addition, RRM2 was involved in ferroptosis, and its expression was up regulated in lung cancer tissues and the LUAD cell lines. Silencing RRM2 can inhibit the proliferation and induce ferroptosis of H1975 cells suggesting that silencing RRM2 could promote ferroptosis in H1975 cells.

Conclusion

Our results revealed RRM2 as a promising biomarker and therapeutic target associated with tumor immune infiltration in patients with LUAD.
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

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

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

Cancer 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

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

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

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

Background

There 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.

Methods

We 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).

Results

Twenty-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.

Conclusion

The 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 registration

Protocol 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

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

Individuals 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

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.
Unicompartmental knee arthroplasty is associated with lower pain levels but inferior range of motion, compared with high tibial osteotomy: a systematic overview of meta-analyses
Authors: Ping Hangyu , Wen Jiaxin , Liu Yubo , Li Haifeng , Wang Xin , Kong Xiangpeng , Chai Wei
Published: September 2022

Background

The purpose of this study was to overview the findings of reported meta-analyses on unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO).

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 (PRISMA 2020) guidelines were followed. Two independent reviewers conducted a literature search of PubMed, Embase, the Web of Science, and the Cochrane Database of Systematic Reviews for meta-analyses comparing UKA and HTO that were published prior to September 2021. Literature screening, data extraction, and article quality appraisal were performed according to the study protocol registered online at PROSPERO (CRD42021279152).

Results

A total of 10 meta-analyses were identified, and different studies reported different results. Five of the seven meta-analyses showed that the proportion of subjects with excellent or good functional results was higher for UKA than for HTO. All three meta-analyses showed that UKA was associated with lower pain levels, and all six of the studies that included an analysis of range of motion (ROM) reported that UKA was inferior to HTO. Four of the eight meta-analyses found that total complication rates were lower for UKA. Only 3 of the 10 meta-analyses found that UKA had lower revision rates. Moreover, in the subgroup analysis, the revision and complication rates of UKA were similar to those of opening-wedge HTO but much lower than those of closing-wedge HTO.

Conclusions

Compared to HTO, UKA was associated with lower pain levels but inferior postoperative ROM. The results were inconclusive regarding whether UKA yielded better knee function scores and lower revision or complication rates than HTO. Accurate identification of indications and appropriate patient selection are essential for treating individuals with OA.
Anatomical characteristics affecting the surgical approach of oblique lateral lumbar interbody fusion: an MR-based observational study
Authors: Han Meng-long , He Wei-hong , He Zhong-yun , Yan Xue-liang , Fang Xiang-jun
Published: September 2022

Background

Oblique lateral lumbar interbody fusion (OLIF) is one of the most widely used lumbar interbody fusion procedures in clinical practice. The aim of this study was to minimize the incidence rate of surgical complications by measuring the anatomical parameters of structures surrounding the working channels of OLIF with 3D COSMIC sequence.

Methods

The MRI examination included conventional MRI sequence and 3D COSMIC sequence. Surgical window, psoas thickness, the transverse diameter of the endplate, and nerve distance were measured to evaluate the anatomical characteristics surrounding the OLIF working channels.

Results

The widths of the natural surgical window at the level of the L2–3, L3–4, and L4–5 intervertebral measured in this study were 16.25 ± 4.22, 15.46 ± 4.64 mm, and 11.71 ± 6.29 mm, respectively. The average thickness of the left psoas major muscle at the level of L2–3, L3–4, and L4–5 intervertebral space was 28.42 ± 5.08 mm, 30.76 ± 5.84 mm, and 31.16 ± 7.72 mm, respectively. The mean value of insertion angle (β) was 45.57° ± 6.19° in L2–3 intervertebral space, 49.90° ± 6.53° in L3–4 intervertebral space, and 43.34° ± 8.88° in L4–5 intervertebral space.

Conclusions

The 3D COSMIC sequences can be used for imaging anatomical assessment before OLIF surgery. In preoperative planning, the 3D COSMIC sequence can be used to measure the relevant parameters mentioned above to optimize the planned surgical approach.
Glut1 deficiency syndrome throughout life: clinical phenotypes, intelligence, life achievements and quality of life in familial cases
Authors: Olivotto Sara , Duse Alessandra , Bova Stefania Maria , Leonardi Valeria , Biganzoli Elia , Milanese Alberto , Cereda Cristina , Bertoli Simona , Previtali Roberto , Veggiotti Pierangelo
Published: September 2022

Background

Glut1 deficiency syndrome (Glut1-DS) is a rare metabolic encephalopathy. Familial forms are poorly investigated, and no previous studies have explored aspects of Glut1-DS over the course of life: clinical pictures, intelligence, life achievements, and quality of life in adulthood.

Clinical, biochemical and genetic data in a cohort of familial Glut1-DS cases were collected from medical records. Intelligence was assessed using Raven’s Standard Progressive Matrices and Raven’s Colored Progressive Matrices in adults and children, respectively. An ad hoc interview focusing on life achievements and the World Health Organization Quality of Life Questionnaire were administered to adult subjects.

Results

The clinical picture in adults was characterized by paroxysmal exercise-induced dyskinesia (PED) (80%), fatigue (60%), low intelligence (60%), epilepsy (50%), and migraine (50%). However, 20% of the adults had higher-than-average intelligence. Quality of Life (QoL) seemed unrelated to the presence of PED or fatigue in adulthood. An association of potential clinical relevance, albeit not statistically significant, was found between intelligence and QoL. The phenotype of familial Glut1-DS in children was characterized by epilepsy (83.3%), intellectual disability (50%), and PED (33%).

Conclusion

The phenotype of familial Glut1-DS shows age-related differences: epilepsy predominates in childhood; PED and fatigue, followed by epilepsy and migraine, characterize the condition in adulthood. Some adults with familial Glut1-DS may lead regular and fulfilling lives, enjoying the same QoL as unaffected individuals. The disorder tends to worsen from generation to generation, with new and more severe symptoms arising within the same family. Epigenetic studies might be useful to assess the phenotypic variability in Glut1-DS.
APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases
Authors: Fernández-Calle Rosalía , Konings Sabine C. , Frontiñán-Rubio Javier , García-Revilla Juan , Camprubí-Ferrer Lluís , Svensson Martina , Martinson Isak , Boza-Serrano Antonio , Venero José Luís , Nielsen Henrietta M. , Gouras Gunnar K. , Deierborg Tomas
Published: September 2022

ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression ofAPOE4is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to howAPOE'ssingle-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on howAPOE'spolymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell–cell communication. We discuss influential factors affecting AD pathology combined with theAPOEgenotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of theAPOEgenotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to theAPOEgenotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in theAPOEfield.
Implementation of continuous temperature monitoring during perioperative care: a feasibility study
Authors: Munday Judy , Sturgess David , Oishi Sabrina , Bendeich Jess , Kearney Allison , Douglas Clint
Published: September 2022

Background

Continuous body temperature monitoring during perioperative care is enabled by using a non-invasive “zero-heat-flux” (ZHF) device. However, rigorous evaluation of whether continuous monitoring capability improves process of care and patient outcomes is lacking. This study assessed the feasibility of a large-scale trial on the impact of continuous ZHF monitoring on perioperative temperature management practices and hypothermia prevention.

Methods

A feasibility study was conducted at a tertiary hospital. Participants included patients undergoing elective surgery under neuraxial or general anesthesia, and perioperative nurses and anesthetists caring for patient participants. Eighty-two patients pre and post introduction of the ZHF device were enrolled. Feasibility outcomes included recruitment and retention, protocol adherence, missing data or device failure, and staff evaluation of intervention feasibility and acceptability. Process of care outcomes included temperature monitoring practices, warming interventions and perioperative hypothermia.

Results

There were no adverse events related to the device and feasibility of recruitment was high (60%). Treatment adherence varied across the perioperative pathway (43 to 93%) and missing data due to electronic transfer issues were identified. Provision of ZHF monitoring had most impact on monitoring practices in the Post Anesthetic Care Unit; the impact on intraoperative monitoring practices was minimal.

Conclusions

Enhancements to the design of the ZHF device, particularly for improved data retention and transfer, would be beneficial prior to a large-scale evaluation of whether continuous temperature monitoring will improve patient outcomes. Implementation research designs are needed for future work to improve the complex area of temperature monitoring during surgery.

 Trial registration

Prospective registration prior to patient enrolment was obtained from the Australian and New Zealand Clinical Trials Registry (ANZCTR) on 16th April 2021 (Registration number: ACTRN12621000438853).
Deep whole genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models
Authors: Deng Niantao , Minoche Andre , Harvey Kate , Li Meng , Winkler Juliane , Goga Andrei , Swarbrick Alex
Published: September 2022

Background

Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDXs) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions.

Results

Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60 × coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance. CSMD1, previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers.

Conclusions

Our WGS data provides a comprehensive genome sequencing resource of these models.