bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of carbohydrate metabolism and lipid profile by methanolic extract of Euphorbia helioscopia and improvement of beta cell function in a type 2 diabetic rat model
Authors: Mustafa Imtiaz , Anwar Haseeb , Irfan Shahzad , Muzaffar Humaira , Ijaz Muhammad Umar
Published: January 2022

Background

Traditional plant-based remedies prescribed to treat diabetes have shown promise in research-based setting. Current research was conducted to examine the antidiabetic and antioxidant effects of methanolic extract of a folk herbal plant Euphorbia helioscopia in a rat model of type 2 diabetes.

Methods

Diabetes was induced in male Wistar rats by administering 5% sucrose in drinking water and cafeteria diet for 8 weeks with subsequent nicotinamide and streptozotocin administration. Diabetic rats were then distributed into four individual groups (n = 8); Positive control (PC; no treatment), standard control (SC; Metformin @ 10 mg/kg bw), treatment 1 (EH1, E. helioscopia methanolic extract @200 mg/kg bw) and treatment 2 (EH2, E. helioscopia methanolic extract @400 mg/kg bw). After 21 days of treatments, the rats were decapitated for blood collection. Serum was evaluated for antidiabetic potential, antioxidant and lipid profile, thyroid hormone, amylin, leptin, and carbohydrate metabolic enzymes. Data were analyzed statistically by one-way analysis of variance (ANOVA).

Results

Serum levels of glucagon, glucose and C-peptide were significantly (P ≤ 0.05) decreased in EH1 (1915.33 ± 98.26a pg/ml, 122.59 ± 2.99a mg/dl, 277.59 ± 28.41a pg/ml respectively) and EH2 (1575.28 ± 56.46a pg/ml, 106.04 ± 5.21a mg/dl, 395.06 ± 42.55a pg/ml respectively) as compared to the PC (3135.78 ± 189.46bpg/ml, 191.24 ± 17.75bmg/dl, 671.70 ± 109.75b pg/ml respectively) group. A similar trend was observed in serum insulin levels in EH1 and EH2 groups. The plant’s methanolic extract effectively reduced the total oxidant status (TOS) and MDA levels in the diabetic rats and increased the total antioxidant capacity (TAC) along with an increased level of SOD, Catalase, Paraoxonase, and arylesterase. The plant extract also induced antihyperlipidemic activity and recovered the thyroid hormones, amylin, and leptin levels to normal. The activity of different carbohydrate metabolic enzymes like Pyruvate Kinase, Glucose 6 phosphate dehydrogenase, phosphofructokinase, and glucokinase has also been restored by the extract treatment.

Conclusion

Current study indicates the antioxidant and antidiabetic potential of E. helioscopia methanolic extract in normalizing the lipid profile, thyroid hormones, amylin, leptin, and carbohydrate metabolism in type 2 diabetic rat model.
Complementary and integrative medicine perspectives among veteran patients and VHA healthcare providers for the treatment of headache disorders: a qualitative study
Authors: Kuruvilla Deena E. , Lindsey Hayley , Grinberg Amy S. , Goldman Roberta E. , Riley Samantha , Baird Sean , Fenton Brenda T. , Sico Jason J. , Damush Teresa M.
Published: January 2022

Objective

To evaluate veteran patient and provider perceptions and preferences on complementary and integrative medicine (CIM) for headache management.

Background

The Veterans Health Administration (VHA) has spearheaded a Whole Health system of care focusing on CIM-based care for veteran patients. Less is known about patients’ and providers’ CIM perceptions and preferences for chronic headache management.

Methods

We conducted semi-structured interviews with 20 veteran patients diagnosed with headache and 43 clinical providers, across 12 VHA Headache Centers of Excellence (HCoE), from January 2019 to March 2020. We conducted thematic and case comparative analyses.

Results

Veteran patients and VHA clinical providers viewed CIM favorably for the treatment of chronic headache. Specific barriers to CIM approaches included: (1) A lack of personnel specialized in specific CIM approaches for timely access, and (2) variation in patient perceptions and responses to CIM treatment efficacy for headache management.

Conclusion

Veteran patients and VHA clinical providers in this study viewed CIM favorably as a safe addition to mainstream headache treatments. Advantages to CIM include favorable adverse effect profiles and patient autonomy over the treatment. By adding more CIM providers and resources throughout the VHA, CIM modalities may be recommended more routinely in the management of veterans with headache.
Analysis of the therapeutic effect of Dimu Ningshen (TCM formula) on attention deficit hyperactivity disorder based on gut microbiota and serum metabolomics
Authors: Tang Kairui , Hao Wenzhi , Mo Xiaowei , Chen Yueyue , Guo Xiaofang , He Liangliang , Wang Binghua , Wang Juxian , Ma Qingyu , Deng Lijuan , Chen Jiaxu
Published: January 2022

Background

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed during adolescence and adulthood. Assessment of the long-term risks of the current drugs for ADHD treatment has been insufficient, and little is known concerning the long-term therapeutic effects of psychostimulants. Commercially available traditional Chinese medicine compound oral preparations [e.g., Dimu Ningshen (DMNS)] have been widely used in the clinical treatment of ADHD, but their influence on the interaction between gut microbes and potential metabolomes remains inconclusive.

Methods

We used a series of behavioral experiments to evaluate the behavioral effects of DMNS on adolescent and adult ADHD rats and used 16S rDNA sequencing of gut microbes and nontarget metabolomics to evaluate the potential pathogenesis of ADHD and explore the biological mechanism of DMNS in ADHD treatment.

Results

For the first time, DMNS was shown to reduce the excessive activity of adult and adolescent ADHD rats and improve the attention deficit of adult ADHD rats. DMNS improved the structural composition of the ADHD gut microbiota and reduced the abundance of Ruminococcaceae_NK4A214_group, Ruminococcus_2, and Eubacterium_nodatum_group. Simultaneously, DMNS increased the circulating levels of peripheral monoamine neurotransmitter precursors (e.g., phenylalanine) and reduced the circulating levels of peripheral fatty acid amides (e.g., oleamide). Finally, the changes in the ADHD serum metabolites were strongly correlated with the gut microbiota.

Conclusion

DMNS has a good effect in treating ADHD, and it may exert this effect by regulating the gut microbiota and affecting metabolites in the peripheral circulation.
Evaluation of statistical illiteracy in Latin American clinicians and the piloting evaluation of a short course across multiple timepoints
Authors: Soto-Mota Adrian , Maravilla Eduardo Carrillo , Fragoso Jose Luis Cárdenas , Cruz Óscar Arturo Lozano , Herrero Alfonso Gulías , Rosales Sergio Ponce De Leon
Published: January 2022

Background

All clinicians require statistical interpretation skills to keep up to date with evidence-based recommendations in their field. However, statistical illiteracy among clinicians is a highly prevalent problem with far-reaching consequences. The few available that report statistical literacy improvements after educational interventions do not measure for how long these benefits last. To estimate statistical illiteracy among Latin-American clinicians across multiple levels of training and to evaluate a 10-h course at multiple timepoints.

Methods

Using an online questionnaire, we evaluated; self-perceived statistical proficiency, scientific literature reading habits and statistical literacy (using an adaptation of the Quick Risk Test). Separately, we evaluated statistical proficiency after a 10-h statistics course in a group of Internal Medicine residents at a tertiary center in Mexico City across multiple time points between November 2020 and February 2021.

Results

Data from 392 clinicians from 9 Latin American countries were analyzed. Most clinicians (85%) failed our adaptation of the Quick Risk Test (mean score = 2.6/10, IQR:1.4). The 10-h course significantly improved the scores of the Internal Medicine Residents (n = 16) from 3.8/10, IQR:1.8 to 8.3/10, IQR:1.4 (p < 0.01). However, scores dropped after one and 2 months to 7.7/10, IQR:1.6 and 6.1 / 10, IQR:2.2, respectively.

Conclusion

Statistical Illiteracy is highly prevalent among Latin American clinicians. Short-term educational interventions are effective but, their benefits quickly fade away. Medical boards and medical schools need to periodically teach and evaluate statistical proficiency to ameliorate these issues.
Student perspectives of extended clinical placements in optometry: a qualitative study
Authors: Kirkman Jacqueline M. , Bentley Sharon A. , Armitage James A. , Wood-Bradley Ryan J. , Woods Craig A.
Published: January 2022

Background

The number of students enrolled in health courses at Australian universities is rising, increasing demand for clinical placements. Optometry students have historically undertaken clinical training in short-block rotations at university-led teaching clinics in metropolitan locations. This is changing, with some optometry programs adopting extended placements. These placements are conducted in community-based practices, with many incorporating a rural component to the training. This study explored factors which influence placement success and satisfaction from the perspective of optometry students.

Methods

Nine focus groups were undertaken with 42 final year optometry students upon completion of a 26-week placement (of which at least half was undertaken in a non-metropolitan area, or area where a shortage of optometrists has been identified). Focus groups were audio recorded and transcribed verbatim. Thematic analysis was conducted according to Braun and Clarke’s 6 step method.

Results

Four key themes were identified during analysis. ‘Changing identity’, related to how the students grew both personally and professionally, with the extended placement being considered the vital component that allowed students to begin thinking of themselves as clinicians. The theme ‘Dealing with complex dynamics and circumstances’ predominantly described instances where the student-supervisor relationship was strained, resulting in high levels of anxiety made worse by a perceived lack of university support. ‘Optometrist under instruction’, related to students feeling that the placement was an ideal opportunity to trial the everyday reality of work without the obligation of an ongoing commitment or employment contract. Finally, the theme ‘Rural practice is more rewarding’, was about a chance to seek different experiences, meet new people and challenge themselves professionally.

Conclusion

While the majority of students enjoyed their placement and felt that it was the key component of their training that equipped them for future practice, it is clear that universities and placement providers must provide both students and supervisors thorough and explicit guidance covering placement expectations. Furthermore, student support systems should be embedded into placement programs to ensure where issues arise, they are dealt with promptly and successfully. It is vital that ongoing professional development and pedagogical training for supervisors underpins continued accreditation.
Still engaged – healthcare staff’s engagement when introducing a new eHealth solution for wound management: a qualitative study
Authors: Fagerström Cecilia , Wickström Hanna , Tuvesson Hanna
Published: January 2022

Background

eHealth solutions have often been considered favourable for improved effectiveness and quality in healthcare services for wound management. Staff engagement related to organisational changes is a key factor for successful development and implementation of a new eHealth solution, like a digital decision support systems (DDSS). It is essential to understand the engagement process in terms of sustainability, wellbeing in staff and efficiency in a long-term perspective. The aim of this study was to describe healthcare staff’s engagement during a 6-month test of an eHealth solution (DDSS) for wound management.

Methods

A qualitative design, including interviews conducted with healthcare staff working with wound management within primary, community and specialist care (n = 11) on two occasions: at the introduction of the solution and after 6 months, when the test period was over. Data were interpreted with qualitative content analysis.

Results

Healthcare staff’s descriptions from a 6-month test of an eHealth solution for wound management can be summarised asEngaging through meaning, but draining. The analysis revealed a result with three subcategories:Having a shared interest is stimulating, Good but not perfectandExciting, but sometimes exhausting.The staff described their engagement as sustained through feelings of meaningfulness when using the eHealth solution, but limited by feelings of exhaustion due to heavy workload and lack of support and understanding from others.

Conclusions

The results indicate that the healthcare staff who tested the eHealth solution described themselves as individuals who easily become engaged when an idea and efforts felt meaningful. The staff needed resources to nourish engagement in their new role when implementing eHealth in the clinical everyday work of wound management. Allocating time and support are important to consider when planning for sustainable implementation of eHealth solutions in healthcare organisations.
Variability in newborn telomere length is explained by inheritance and intrauterine environment
Authors: Chen Li , Tan Karen Mei Ling , Gong Min , Chong Mary F. F. , Tan Kok Hian , Chong Yap Seng , Meaney Michael J. , Gluckman Peter D. , Eriksson Johan G. , Karnani Neerja
Published: January 2022

Background

Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus.

Methods

Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26–28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied.

Results

Longer maternal TL (β = 0.14, P = 1.99E−05) and higher paternal age (β = 0.10, P = 3.73E−03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: Pmeta = 5.95E−08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother’s TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL.

Conclusions

Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors.

Trial registration

ClinicalTrials.gov, NCT01174875. Registered on 1 July 2010
The diagnosis and molecular epidemiology investigation of avian hepatitis E in Shandong province, China
Authors: Liu Kuihao , Zhao Yiran , Zhao Jun , Geng Ningwei , Meng Fanliang , Wang Siqi , Li Jing , Zhong Zhaobing , Zhu Liya , Liu Sidang , Li Ning
Published: January 2022

Background

Avian hepatitis E virus (HEV) is the pathogenic agent of big liver and spleen disease (BLS) and of hepatitis-splenomegaly syndrome (HSS) in chickens, which have caused economic losses to the poultry industry in China. In this study, 18 samples of BLS chickens were collected to reveal the molecular epidemiological characteristics of avian HEV in the province of Shandong, China.

Results

Gross and microscopic lesions of clinical samples were observed; then, virology detection and genetic analysis of avian HEV were performed. The results showed that there was significant swelling and rupture in the liver and that the spleen was enlarged. Microscopic lesions demonstrated obvious hemorrhage in the liver, with infiltration of heterophilic granulocytes, lymphocytes, and macrophages, as well as the reduction of lymphocytes in the spleen. Eleven of the 18 samples were positive for avian HEV, with a positive rate of 61.11%. More importantly, all avian HEV-positive samples were mixed infections: among these, the mixed infections of avian HEV and chicken infectious anemia virus (CIAV) and avian HEV and fowl adenovirus (FAdV) were the most common. Furthermore, the genetic evolution analysis showed that all avian HEV strains obtained here did not belong to the reported 4 genotypes, thus constituting a potential novel genotype.

Conclusions

These results of this study further enrich the epidemiological data on avian HEV in Shandong, prove the genetic diversity of avian HEV in China, and uncover the complex mixed infections of avian HEV clinical samples.
Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer
Authors: Li Longxia , He Di , Guo Qianqian , Zhang Zhiyoung , Ru Dan , Wang Liting , Gong Ke , Liu Fangfang , Duan Yourong , Li He
Published: January 2022

Background

Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility.

Results

Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages.

Conclusion

Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.

Graphical Abstract
The PB1 gene from H9N2 avian influenza virus showed high compatibility and increased mutation rate after reassorting with a human H1N1 influenza virus
Authors: Cui Hongrui , Che Guangsheng , de Jong Mart C. M. , Li Xuesong , Liu Qinfang , Yang Jianmei , Teng Qiaoyang , Li Zejun , Beerens Nancy
Published: January 2022

Background

Reassortment between human and avian influenza viruses (AIV) may result in novel viruses with new characteristics that may threaten human health when causing the next flu pandemic. A particular risk may be posed by avian influenza viruses of subtype H9N2 that are currently massively circulating in domestic poultry in Asia and have been shown to infect humans. In this study, we investigate the characteristics and compatibility of a human H1N1 virus with avian H9N2 derived genes.

Methods

The polymerase activity of the viral ribonucleoprotein (RNP) complex as combinations of polymerase-related gene segments derived from different reassortment events was tested in luciferase reporter assays. Reassortant viruses were generated by reverse genetics. Gene segments of the human WSN-H1N1 virus (A/WSN/1933) were replaced by gene segments of the avian A2093-H9N2 virus (A/chicken/Jiangsu/A2093/2011), which were both the Hemagglutinin (HA) and Neuraminidase (NA) gene segments in combination with one of the genes involved in the RNP complex (either PB2, PB1, PA or NP). The growth kinetics and virulence of reassortant viruses were tested on cell lines and mice. The reassortant viruses were then passaged for five generations in MDCK cells and mice lungs. The HA gene of progeny viruses from different passaging paths was analyzed using Next-Generation Sequencing (NGS).

Results

We discovered that the avian PB1 gene of H9N2 increased the polymerase activity of the RNP complex in backbone of H1N1. Reassortant viruses were able to replicate in MDCK and DF1 cells and mice. Analysis of the NGS data showed a higher substitution rate for the PB1-reassortant virus. In particular, for the PB1-reassortant virus, increased virulence for mice was measured by increased body weight loss after infection in mice.

Conclusions

The higher polymerase activity and increased mutation frequency measured for the PB1-reassortant virus suggests that the avian PB1 gene of H9N2 may drive the evolution and adaptation of reassortant viruses to the human host. This study provides novel insights in the characteristics of viruses that may arise by reassortment of human and avian influenza viruses. Surveillance for infections with H9N2 viruses and the emergence of the reassortant viruses in humans is important for pandemic preparedness.
The evaluation of podiatrists, with knowledge and training in diagnostic musculoskeletal ultrasound, to describe sonographic images of diabetic foot wounds in the United Kingdom and Australia
Authors: Dando Charlotte , Lane Georgia , Bowen Catherine , Henshaw Frances
Published: January 2022

Aims

Currently, wound management decisions are based largely on visual observations such as photographs, descriptors or measurements which can lack detail and do not always capture the sub‐wound area. A previous case series suggests that there is benefit in using ultrasound imaging (USI) to evaluate diabetic foot ulcers (DFU) at point‐of‐care, however no guidance exists to inform its use. This scoping exercise explores the capacity of podiatrists with experience in interpreting musculoskeletal structures using USI to interpret sonographic images of DFU.

Methods

Following a short briefing session, podiatrists with previous musculoskeletal (MSK) USI training were asked to review and report on previously recorded static sonographic images (n = 8) of active DFU. Content analysis was utilised to identify recurring keywords within the podiatrists' reports which were coded and assigned to categories to gain context to the data.

Results

Seven podiatrists participated in the study. Four categories were constructed for the purposes of analysis:

Frequency of reporting, 2) Language used in reporting, 3) Observations, 4) Clinical impression

Frequently, the reported findings between podiatrists were found to be similar, especially those related to bone morphology. However greater variability was seen in the reporting of wound specific soft‐tissue observations.

Conclusion

This scoping exercise has shown that podiatrists can translate their existing USI skills to make rudimentary reports on clinical findings in DFU. All participants were consistently able to identify and describe characteristics associated with DFU from a single b mode static wound ultrasound image. Findings from this investigation can be used as a foundation for further work to establish accuracy and reliability to validate DFU sonography. In conjunction the development of protocols and training materials will enable the adoption of USI to assess DFU in clinical practice. This will in turn, contribute to improved patient care and establish a new paradigm for wound surveillance which is translatable to other wound types.
Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation
Authors: Tang Yu Hin , Rockstroh Anja , Sokolowski Kamil A. , Lynam Layla-Rose , Lehman Melanie , Thompson Erik W. , Gregory Philip A. , Nelson Colleen C. , Volpert Marianna , Hollier Brett G.
Published: January 2022

Background

Triple-negative breast cancers (TNBC) have a relatively poor prognosis and responses to targeted therapies. Between 25 and 39% of TNBCs are claudin-low, a poorly differentiated subtype enriched for mesenchymal, stem cell and mitogen-activated signaling pathways.
We investigated the role of the cell-surface co-receptor NRP1 in the biology of claudin-low TNBC.

Methods

The clinical prognostic value of NRP1 was determined by Kaplan–Meier analysis. GSVA analysis of METABRIC and Oslo2 transcriptomics datasets was used to correlate NRP1 expression with claudin-low gene signature scores. NRP1 siRNA knockdown was performed in MDA-MB-231, BT-549, SUM159 and Hs578T claudin-low cells and proliferation and viability measured by live cell imaging and DNA quantification. In SUM159 orthotopic xenograft models using NSG mice, NRP1 was suppressed by shRNA knockdown or systemic treatment with the NRP1-targeted monoclonal antibody Vesencumab. NRP1-mediated signaling pathways were interrogated by protein array and Western blotting.

Results

High NRP1 expression was associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts. NRP1 was over-expressed specifically in claudin-low clinical samples and cell lines, and NRP1 knockdown reduced proliferation of claudin-low cells and prolonged survival in a claudin-low orthotopic xenograft model. NRP1 inhibition suppressed expression of the mesenchymal and stem cell markers ZEB1 and ITGA6, respectively, compromised spheroid-initiating capacity and exerted potent anti-tumor effects on claudin-low orthotopic xenografts (12.8-fold reduction in endpoint tumor volume). NRP1 was required to maintain maximal RAS/MAPK signaling via EGFR and PDGFR, a hallmark of claudin-low tumors.

Conclusions

These data implicate NRP1 in the aggressive phenotype of claudin-low breast cancer and offer a novel targeted therapeutic approach to this poor prognosis subtype.
LncRNA IPW inhibits growth of ductal carcinoma in situ by downregulating ID2 through miR-29c
Authors: Deshpande Ravindra Pramod , Sharma Sambad , Liu Yin , Pandey Puspa Raj , Pei Xinhong , Wu Kerui , Wu Shih-Ying , Tyagi Abhishek , Zhao Dan , Mo Yin-Yuan , Watabe Kounosuke
Published: January 2022

Background

Ductal carcinoma in situ (DCIS) of breast is the noninvasive lesion that has propensity to progress to the malignant form. At present, it is still unknown which lesions can potentially progress to invasive forms. In this study, we aimed to identify key lncRNAs involved in DCIS growth.

Methods

We employ disease-related lncProfiler array to identify IPW in specimens of DCIS and matching control samples and validate the observations in three DCIS-non-tumorigenic cell lines. Further, we examine the mechanism of IPW action and the downstream signaling in in vitro and in vivo assays. Importantly, we screened a library containing 390 natural compounds to identify candidate compound selectively inhibiting IPW low DCIS cells.

Results

We identified lncRNA IPW as a novel tumor suppressor critical for inhibiting DCIS growth. Ectopic expression of IPW in DCIS cells strongly inhibited cell proliferation, colony formation and cell cycle progression while silencing IPW in primary breast cells promoted their growth. Additionally, orthotropic implantation of cells with ectopic expression of IPW exhibited decreased tumor growth in vivo. Mechanistically, IPW epigenetically enhanced miR-29c expression by promoting H3K4me3 enrichment in its promoter region. Furthermore, we identified that miR-29c negatively regulated a stemness promoting gene, ID2, and diminished self-renewal ability of DCIS cells. Importantly, we screened a library containing 390 natural compounds and identified toyocamycin as a compound that selectively inhibited the growth of DCIS with low expression of IPW, while it did not affect DCIS with high IPW expression. Toyocamycin also suppressed genes associated with self-renewal ability and inhibited DCIS growth in vivo.

Conclusion

Our findings revealed a critical role of the IPW-miR-29c-ID2 axis in DCIS formation and suggested potential clinical use of toyocamycin for the treatment of DCIS.
Microbiota of the prostate tumor environment investigated by whole-transcriptome profiling
Authors: Salachan Paul Vinu , Rasmussen Martin , Fredsøe Jacob , Ulhøi Benedicte , Borre Michael , Sørensen Karina Dalsgaard
Published: January 2022

Background

With over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. While cancer in general is considered a disease of the human genome, there is a growing body of evidence suggesting that changes to the healthy microbiota could play a vital role in cancer development, progression, and/or treatment outcome.

Methods

Using a metatranscriptomic approach, we annotated the microbial reads obtained from total RNA sequencing of 106 prostate tissue samples from 94 PCa patients (discovery cohort). We investigated microbial dysbiosis associated with PCa by systematically comparing the microbiomes between benign and malignant tissue samples, between less vs. more-aggressive PCa, and between patients who had biochemical recurrence as opposed to those who did not. We further performed differential gene expression and cell type enrichment analysis to explore the host transcriptomic and cellular responses to selected microbial genera. A public dataset (GSE115414) of total RNA sequencing reads from 24 prostate tissue samples (8 benign and 16 malignant) served as the validation cohort.

Results

We observed decreased species diversity and significant under-representation ofStaphylococcus saprophyticusandVibrio parahaemolyticus, as well as significant over-abundance ofShewanellain malignant as compared to benign prostate tissue samples in both the discovery (p< 0.01) and validation (p< 0.05) cohorts. In addition, we identifiedMicrobacteriumspecies (p< 0.01) to be significantly over-abundant in pathologically advanced T3 tumors compared to T2 in the discovery cohort. Malignant samples having high vs. lowShewanellacounts were associated with downregulated Toll-like receptor signaling pathways and decreased enrichment of dendritic cells. Malignant samples having low vs. highV. parahaemolyticuscounts were enriched for olfactory transduction and drug metabolism pathways. Finally, malignant samples were enriched for M1 and M2 macrophages as compared to benign tissue samples.

Conclusions

The results from this exploratory study support the existence of an important biological link between the prostate microbiota and PCa development/progression. Our results highlightShewanella,V. parahaemolyticus, andMicrobacterium sp.as interesting candidates for further investigation of their association with PCa.
Fifteen years of enzyme replacement therapy for mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome): a case report
Authors: Andrade Isadora , Ribeiro River , Carneiro Zumira A. , Giugliani Roberto , Pereira Catarina , Cozma Claudia , Grinberg Daniel , Vilageliu Lluïsa , Lourenco Charles M.
Published: January 2022

Background

Mucopolysaccharidosis VI, or Maroteaux–Lamy disease, is an autosomal recessive disease characterized by deficiency of the enzyme arylsulfatase B in the lysosomal catabolism of glycosaminoglycans. Due to reduced (or even null) enzyme activity, glycosaminoglycans (mainly dermatan sulfate) accumulates, leading to a multisystemic disease. Mucopolysaccharidosis VI induces reduced growth, coarse face, audiovisual deficits, osteoarticular deformities, and cardiorespiratory issues, hampering the quality of life of the patient. Enzyme replacement therapy with galsulfase (Naglazyme, BioMarin Pharmaceuticals Inc., USA) is the specific treatment for this condition. Although studies have shown that enzyme replacement therapy slows the progression of the disease, the effects of long-term enzyme replacement therapy remain poorly understood.

Case presentation

A 29-year-old, Caucasian, male patient diagnosed with mucopolysaccharidosis VI was treated with enzyme replacement therapy for over 15 years. Enzyme replacement therapy was initiated when patient was 13 years old. The patient evolved multiplex dysostosis, carpal tunnel syndrome, thickened mitral valve, and hearing and visual loss.

Conclusions

Although enzyme replacement therapy did not prevent the main signs of mucopolysaccharidosis VI, it slowed their progression. Additionally, enzyme replacement therapy was associated with a longer survival compared with the untreated affected sibling. Taken together, the results indicate that enzyme replacement therapy positively modified the course of the disease.
Robust error estimation based on factor-graph models for non-line-of-sight localization
Authors: Vanli O. Arda , Taylor Clark N.
Published: January 2022

This paper presents a method to estimate the covariances of the inputs in a factor-graph formulation for localization under non-line-of-sight conditions. A general solution based on covariance estimation and M-estimators in linear regression problems, is presented that is shown to give unbiased estimators of multiple variances and are robust against outliers. An iteratively re-weighted least squares algorithm is proposed to jointly compute the proposed variance estimators and the state estimates for the nonlinear factor graph optimization. The efficacy of the method is illustrated in a simulation study using a robot localization problem under various process and measurement models and measurement outlier scenarios. A case study involving a Global Positioning System based localization in an urban environment and data containing multipath problems demonstrates the application of the proposed technique.
The prevalence, risk factors and outcomes of anaemia in South African pregnant women: a systematic review and meta-analysis
Authors: Dorsamy Vinogrin , Bagwandeen Chauntelle , Moodley Jagidesa
Published: January 2022

Background

Anaemia is associated with maternal and perinatal morbidity and mortality. The pooled prevalence of anaemia in the South African (SA) pregnant population was ascertained by systematically reviewing available literature. Severity, risk factors (HIV, tuberculosis, race, province, year of study), maternal morbidity and mortality (hypertensive disorders of pregnancy), birth outcomes (including low birth weight) and supplementation during pregnancy were also described.

Methods

Eligible studies reported on haemoglobin concentration or prevalence of anaemia in a SA pregnant population and were available in full text. Case-control and estimation studies were excluded with no restriction on the date of publication. PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS were searched, using the keywords ‘anaemia’, ’haemoglobin’, ‘pregnancy’, ‘South Africa’. Risk of bias was conducted using the Hoy tool and the Doi plot and LFK ratio. Overall study quality was assessed using the GRADE tool. Due to heterogeneity amongst studies subgroup analyses were performed (random effects and quality effects model) using MetaXL addon tool for Microsoft Excel.

Results

The initial search yielded 7010 articles and 26 were selected for inclusion. Twenty studies were cross-sectional, three were longitudinal and one a randomised control trial. Studies ranged in publication year from 1969 to 2020. The pooled prevalence of anaemia in pregnant women in SA was determined to be 31% (95% CI, 23–40%). Hypertensive disorders of pregnancy and low birth weight were associated with anaemia. While iron deficiency was reported as the main cause, other risk factors included HIV and other infections.

Discussion

Limitations

There was limited data reporting on prevalence of anaemia and direct maternal and foetal outcomes. Heterogeneity amongst studies was not explained by subgroup analysis. Majority of cross-sectional study designs reduced the ability to infer causality.

Interpretation

While the prevalence of anaemia remains high and of concern, risk factors are varied. Iron deficiency is still common but the presence of comorbidities also contributes to anaemia and should not be ignored. More longitudinal research into associations between anaemia and birth outcomes is needed due to a lack of available evidence.

Systematic review registration

PROSPERO 2020:CRD42020157191.
Instruments for measuring incidents related to patient safety in the context of paediatric intensive care—protocol for a scoping review
Authors: de Oliveira Helga Catarina Santos Alves , Marques Ricardo Rafael , dos Santos Curado Maria Alice , Gaspar Maria Filomena Mendes , dos Santos Sousa Paulo Jorge
Published: January 2022

Background

Patient safety is a fundamental principle of health care but is one of the biggest challenges currently faced and a serious public health problem, since the occurrence of adverse events is probably one of the main causes of morbidity and mortality worldwide. The vulnerability of the paediatric population, combined with the potentially dangerous context of intensive care, makes Paediatric Intensive Care Units services of particular complexity in matters of safety, where there is a greater likelihood of incidents with serious consequences. It is agreed that research on the topic of PS should start with the measuring of different types of harm that exist in the contexts, to identify high-risk areas and define priorities. For this, it is necessary to resort to a multiplicity of valid, reliable and specific measurement instruments and to learn their advantages and limitations. The objective of this review will be to identify and map in scientific literature the instruments for measuring incidents related to patient safety applicable in the context of paediatric intensive care.

Methods

This review will cover studies and documents that refer to all measurement instruments used in the field of patient safety in a context of paediatric intensive care. Quantitative, qualitative, or mixed nature published studies, as well as grey literature, produced in the last 5 years and relevant to the topic will be included, in Portuguese, English or Spanish languages. The sources of information include several databases (such as MEDLINE, CINAHL, Cochrane Library, JBI Databases) and sources relevant to grey literature. Two reviewers will independently screen all citations, full-text articles and abstract data. The extracted data, after being organised in the extraction table, will be mapped in a descriptive and logical way, taking into account the defined review questions.

Discussion

The mapping of the tools in these protocols will allow to summarise the most widely used instruments, to know their specificities and to guide researchers to use the most appropriate measurement tools for their context, specifically, in paediatric intensive care.

Systematic review registration

Open Science Framework (osf.io/b5m7j).
Designing of an open innovation model in science and technology parks
Authors: Bayat Pari , Daraei Mehry , Rahimikia Amin
Published: January 2022

The main purpose of this research is to design and test an open innovation model in science and technology parks through a mixed exploratory approach. The data collection tool in the qualitative section is a semi-structured interview with 15 experts in the field of science and technology parks. Purposive sampling was used until theoretical saturation is achieved. The grounded theory was used to coding the interviews. As a result of open, axial, and selective coding in MAXQDA, 1551 free codes, 202 concepts, 73 sub-codes, and 21 main codes extracted. These codes categorized in six themes of causal conditions, central phenomenon, strategies, contextual conditions, intervening conditions, and outcomes. Initial questionnaire was administrated among 516 experts and managers of science and technology parks in Tehran province and affiliated companies. Confirmatory factor analyses showed high model fit with CFI equal to .93 and high internal consistency for the total score equal to .98. The results of this study showed that the proposed model of open innovation in science and technology parks in Iran has a good fit.
Numerical Analysis of the Effect of Afterburning on Damage to the Concrete Structure Under Interior Explosion
Authors: Kim Hak Jun , Hwang Kyuwan , Yoon Yeo Hun , Lee Hyun-Jin
Published: January 2022

A numerical simulation was performed to analyze how afterburning affects damage to a concrete structure when an explosive detonates inside a room. TNT was used as the explosive for the interior explosion. A reduced scale structure of a Korean apartment room was constructed with reinforced concrete and used as the target room for this research. Interior explosion experiments were performed using TNT 2 kg and TNT 3 kg explosives, to obtain data to verify and calibrate the numerical model. The numerical model was constructed to precisely simulate these interior explosions, especially considering the effect of afterburning, which is a significant phenomenon in enclosed spaces. Numerical simulations were performed with and without the effect of afterburning, and compared with the experiment results. The results showed that the numerical model could well simulate the effects of afterburning in an interior explosion, and that afterburning effects must be considered to more accurately analyze the damage to concrete structures.
A systematic review on trends in using Moodle for teaching and learning
Authors: Gamage Sithara H. P. W. , Ayres Jennifer R. , Behrend Monica B.
Published: January 2022

Background

The Moodle Learning Management System (LMS) is widely used in online teaching and learning, especially in STEM education. However, educational research on using Moodle is scattered throughout the literature. Therefore, this review aims to summarise this research to assist three sets of stakeholders—educators, researchers, and software developers. It identifies: (a) how and where Moodle has been adopted; (b) what the concerns, trends, and gaps are to lead future research and software development; and (c) innovative and effective methods for improving online teaching and learning.

The review used the 4-step PRISMA-P process to identify 155 suitable journal articles from 104 journals in 55 countries published from January 2015 to June 2021. The database search was conducted with Scopus and Web of Science. Insights into the educational use of Moodle were determined through bibliometric analysis with Vosviewer outputs and thematic analysis.

Results

This review shows that Moodle is mainly used within University STEM disciplines and effectively improves student performance, satisfaction, and engagement. Moodle is increasingly being used as a platform for adaptive and collaborative learning and used to improve online assessments. The use of Moodle is developing rapidly to address academic integrity, ethics, and security issues to enhance speed and navigation, and incorporate artificial intelligence.

Conclusion

More qualitative research is required on the use of Moodle, particularly investigating educators’ perspectives. Further research is also needed on the use of Moodle in non-STEM and non-tertiary disciplines. Further studies need to incorporate educational theories when designing courses using the Moodle platform.
Segmentation-guided multi-modal registration of liver images for dose estimation in SIRT
Authors: Tang Xikai , Jafargholi Rangraz Esmaeel , Heeren Richard’s , Coudyzer Walter , Maleux Geert , Baete Kristof , Verslype Chris , Gooding Mark J. , Deroose Christophe M. , Nuyts Johan
Published: January 2022

Purpose

Selective internal radiation therapy (SIRT) requires a good liver registration of multi-modality images to obtain precise dose prediction and measurement. This study investigated the feasibility of liver registration of CT and MR images, guided by segmentation of the liver and its landmarks. The influence of the resulting lesion registration on dose estimation was evaluated.

Methods

The liver segmentation was done with a convolutional neural network (CNN), and the landmarks were segmented manually. Our image-based registration software and its liver-segmentation-guided extension (CNN-guided) were tuned and evaluated with 49 CT and 26 MR images from 20 SIRT patients. Each liver registration was evaluated by the root mean square distance (RMSD) of mean surface distance between manually delineated liver contours and mass center distance between manually delineated landmarks (lesions, clips, etc.). The root mean square of RMSDs (RRMSD) was used to evaluate all liver registrations. The CNN-guided registration was further extended by incorporating landmark segmentations (CNN&LM-guided) to assess the value of additional landmark guidance. To evaluate the influence of segmentation-guided registration on dose estimation, mean dose and volume percentages receiving at least 70 Gy (V70) estimated on the 99mTc-labeled macro-aggregated albumin (99mTc-MAA) SPECT were computed, either based on lesions from the reference 99mTc-MAA CT (reference lesions) or from the registered floating CT or MR images (registered lesions) using the CNN- or CNN&LM-guided algorithms.

Results

The RRMSD decreased for the floating CTs and MRs by 1.0 mm (11%) and 3.4 mm (34%) using CNN guidance for the image-based registration and by 2.1 mm (26%) and 1.4 mm (21%) using landmark guidance for the CNN-guided registration. The quartiles for the relative mean dose difference (the V70 difference) between the reference and registered lesions and their correlations [25th, 75th; r] are as follows: [− 5.5% (− 1.3%), 5.6% (3.4%); 0.97 (0.95)] and [− 12.3% (− 2.1%), 14.8% (2.9%); 0.96 (0.97)] for the CNN&LM- and CNN-guided CT to CT registrations, [− 7.7% (− 6.6%), 7.0% (3.1%); 0.97 (0.90)] and [− 15.1% (− 11.3%), 2.4% (2.5%); 0.91 (0.78)] for the CNN&LM- and CNN-guided MR to CT registrations.

Conclusion

Guidance by CNN liver segmentations and landmarks markedly improves the performance of the image-based registration. The small mean dose change between the reference and registered lesions demonstrates the feasibility of applying the CNN&LM- or CNN-guided registration to volume-level dose prediction. The CNN&LM- and CNN-guided registrations for CTs can be applied to voxel-level dose prediction according to their small V70 change for most lesions. The CNN-guided MR to CT registration still needs to incorporate landmark guidance for smaller change of voxel-level dose estimation.