bluuebunny/crossref_metadata_2025 huggingface dataset:
Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study
Authors: Li Shuai , Hua Xinyang
Published: February 2021

Background

Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death. However, whether these relationships are causal is not well known; neither for the relationships between COVID-19 severe illness and other common lifestyle factors, such as physical activity and alcohol consumption.

Methods

Genome-wide significant genetic variants associated with body mass index (BMI), lifetime smoking, physical activity and alcohol consumption identified by large-scale genome-wide association studies (GWAS) of up to 941,280 individuals were selected as instrumental variables. Summary statistics of the genetic variants on severe illness of COVID-19 were obtained from GWAS analyses of up to 6492 cases and 1,012,809 controls. Two-sample Mendelian randomisation analyses were conducted.

Results

Both per-standard deviation (SD) increase in genetically predicted BMI and lifetime smoking were associated with about two-fold increased risks of severe respiratory COVID-19 and COVID-19 hospitalization (all P < 0.05). Per-SD increase in genetically predicted physical activity was associated with decreased risks of severe respiratory COVID-19 (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.05, 0.74; P = 0.02), but not with COVID-19 hospitalization (OR = 0.44; 95% CI 0.18, 1.07; P = 0.07). No evidence of association was found for genetically predicted alcohol consumption. Similar results were found across robust Mendelian randomisation methods.

Conclusions

Evidence is found that BMI and smoking causally increase and physical activity might causally decrease the risk of COVID-19 severe illness. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness and its public health value in fighting against COVID-19 pandemic.
Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study
Authors: Klose Hans , Chin Kelly M. , Ewert Ralf , Gall Henning , Parambil Joseph , Poch David , Seyfarth Hans-Jürgen , Axelsen Lene N. , Hsu Schmitz Shu-Fang , Stein Claudia , Preston Ioana R.
Published: February 2021

Background

The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov).

Methods

PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration.

Results

All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses.

Conclusions

Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.
Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach
Authors: Lezmi Guillaume , Vibhushan Shamila , Bevilaqua Claudia , Crapart Nicolas , Cagnard Nicolas , Khen-Dunlop Naziha , Boyle-Freyssaut Christine , Hadchouel Alice , Delacourt Christophe
Published: February 2021

Background

The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.

Aim

This study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms.

Methods

Tissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser capture microdissection (LCM). Transcriptomic analyses were performed and the results were confirmed by RT-PCR and immunohistochemistry in independent samples.

Results

After controlling for RNA quality, we analysed the transcriptomes of six cystic areas and five control areas. In total, 393 transcripts were differentially expressed in the epithelium, between CCAM and control areas. The most highly redundant genes involved in biological functions and signalling pathways differentially expressed between CCAM and control epithelium includedTGFB2, TGFBR1, andMAP 2 K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples thatTGFBR1was more strongly expressed in CCAM than in control tissues (p < 0.03). Immunohistochemistry analysis showed TGFBR1 (p = 0.0007) and TGFB2 (p < 0.02) levels to be significantly higher in the epithelium of CCAM than in that of control tissues.

Conclusions

This compartmentalised transcriptomic analysis of the epithelium of macrocystic lung malformations identified a dysregulation of TGFB signalling at the mRNA and protein levels, suggesting a possible role of this pathway in CCAM pathogenesis.

Trial registration

ClinicalTrials.gov Identifier:NCT01732185.
LINC00963 affects the development of colorectal cancer via MiR-532-3p/HMGA2 axis
Authors: Ye Jinjun , Liu Jidong , Tang Tao , Xin Le , Bao Xing , Yan Yukuang
Published: February 2021

Background

LINC00963 is high-expressed in various carcinomas, but its expression and function in colorectal cancer (CRC) have not been explored. This study explored the role and mechanism of LINC00963 in CRC.

Methods

The expression of LINC00963 in CRC and its relationship with prognosis were examined by starBase and survival analysis. The effects of LINC00963, miR-532-3p and HMGA2 on the biological characteristics and EMT-related genes of CRC cells were studied by RT-qPCR, CCK-8, clone formation experiments, flow cytometry, scratch test, Transwell, and Western blot. Xenograft assay and immunohistochemistry were performed to verify the effect of LINC00963 on tumor growth. The correlation among LINC00963, miR-532-3p, and HMGA2 was analyzed by bioinformatics analysis, luciferase assay, and Pearson test.

Results

LINC00963 was high-expressed in CRC, and this was associated with poor prognosis of CRC. Silencing LINC00963 inhibited the activity, proliferation, migration, and invasion of CRC cells, MMP-3 and MMP-9 expressions, moreover, it also blocked cell cycle progression, and inhibited tumor growth and Ki67 expression. However, overexpression of LINC00963 showed the opposite effects to silencing LINC00963. LINC00963 targeted miR-532-3p to regulate HMGA2 expression. Down-regulation of miR-532-3p promoted cell proliferation, migration and invasion, and expressions of MMP-3 and MMP-9, and knockdown of HMGA2 reversed the effect of miR-532-3p inhibitor. Up-regulation of miR-532-3p inhibited the biological functions of CRC cells, and overexpression of HMGA2 reversed the miR-532-3p mimic effect.

Conclusion

LINC00963 affects the development of CRC through the miR-532-3p/HMGA2 axis.
circ-ANXA7 facilitates lung adenocarcinoma progression via miR-331/LAD1 axis
Authors: Wang Yu
Published: February 2021

Background

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, with a poor prognosis. The roles of circular RNAs (circRNAs) in tumors have been initially clarified. In this study, we probed into the functions and underlying molecular mechanisms of circ-ANXA7 in LUAD.

Methods

According to circRNA microarray analysis based on 40 pairs of LUAD tissues and non-tumor tissues, a novel circ-ANXA7 was up-regulated in LUAD, which was verified in LUAD tissues and cells by RT-qPCR. Correlation between its expression and clinical features of LUAD was analyzed. When transfected with sh-circ-ANXA7, proliferation, invasion, and migration of LUAD cells were determined by a series of functional assays. Furthermore, tumor growth was investigated in nude mice injected with sh-circ-ANXA7. Dual luciferase report and gain and loss assays were used to confirm the relationships between circ-ANXA7 and miR-331, miR-331 and LAD1.

Results

circ-ANXA7 was up-regulated in LUAD tissues and cells. Its high expression promoted proliferation, migration, and invasion of LUAD cells as well as tumor growth. High circ-ANXA7 expression usually predicted a poorer prognosis for LUAD patients. Furthermore, circ-ANXA7 could accelerate proliferation and invasion of LUAD cells by targeting miR-331. miR-331 directly bound to the 3′-UTR of LAD1. LAD1 induced proliferation and invasion of LUAD cells, which was reversed after co-transfection with circ-ANXA7 knockdown. LAD1 expression could be an independent prognostic marker for LUAD by univariate and multivariate analysis.

Conclusions

Our research identified a novel circ-ANXA7 for LUAD, which could facilitate proliferation, migration, and invasion of LUAD cells by miR-331/ LAD1 axis. circ-ANXA7 could become a promising prognosis and treatment target for LUAD.
Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer
Authors: Long Fei , Lin Zhi , Li Liang , Ma Min , Lu Zhixing , Jing Liang , Li Xiaorong , Lin Changwei
Published: February 2021

Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.
2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy
Authors: Zhao Jiayan , Wu Hang , Zhao Jiulong , Yin Yichen , Zhang Zhilun , Wang Shige , Lin Kun
Published: February 2021

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg–Mn–Al layered double hydroxides (LDH) clay with MoS2doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2and imaging and catalytic functions of Mg–Mn–Al LDH. The designed LDH-MoS2(LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg–Mn–Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.
Peer driven or driven peers? A rapid review of peer involvement of people who use drugs in HIV and harm reduction services in low- and middle-income countries
Authors: Chang Judy , Shelly Shaun , Busz Machteld , Stoicescu Claudia , Iryawan Arif Rachman , Madybaeva Dinara , de Boer Yuri , Guise Andy
Published: February 2021

Introduction

Peer involvement of people who use drugs within HIV and harm reduction services is widely promoted yet under-utilised. Alongside political and financial barriers is a limited understanding of the roles, impacts, contexts and mechanisms for peer involvement, particularly in low- and middle-income settings. We conducted a rapid review of available literature on this topic.

Methods

Within a community-academic partnership, we used a rapid review approach, framed by realist theory. We used a network search strategy, focused on core journals and reference lists of related reviews. Twenty-nine studies were included. We developed thematic summaries framed by a realist approach of exploring interventions, their mechanisms, outcomes and how they are shaped by contexts.

Results

Reported outcomes of peer involvement included reduced HIV incidence and prevalence; increased service access, acceptability and quality; changed risk behaviours; and reduced stigma and discrimination. Mechanisms via which these roles work were trust, personal commitment and empathy, using community knowledge and experience, as well as ‘bridge’ and ‘role model’ processes. Contexts of criminalisation, under-resourced health systems, and stigma and discrimination were found to shape these roles, their mechanisms and outcomes. Though contexts and mechanisms are little explored within the literature, we identified a common theme across contexts, mechanisms and outcomes. Peer outreach interventions work through trust, community knowledge and expertise, and ‘bridge’ mechanisms (M) to counter criminalisation and constraining clinic and service delivery environments (C), contributing towards changed drug-using behaviours, increased access, acceptability and quality of harm reduction services and decreased stigma and discrimination (O).

Conclusion

Peer involvement in HIV and harm reduction services in low- and middle-income settings is linked to positive health outcomes, shaped by contexts of criminalisation, stigma, and resource scarcity. However, peer involvement is under-theorised, particularly on how contexts shape mechanisms and ultimately outcomes. Efforts to study peer involvement need to develop theory and methods to evaluate the complex mechanisms and contexts that have influence. Finally, there is a need to expand the range of peer roles, to embrace the capacities and expertise of people who use drugs.
Dietary supplement of Yunkang 10 green tea and treadmill exercise ameliorate high fat diet induced metabolic syndrome of C57BL/6 J mice
Authors: Zhang Yanzhong , Gu Mingxing , Wang Ruru , Li Menwan , Li Daxiang , Xie Zhongwen
Published: February 2021

Background

Diet and exercise play important roles in ameliorating metabolic syndrome. Yunkang 10 (Camellia sinensis var. assamica) is a most cultivated tea variety for making tea in the Southwestern China. Currently, there is no report of healthy effects of Yunkang 10 green tea (YKGT) and treadmill exercise (Ex) on high fat diet induced metabolic syndrome (MetS). We aimed to investigate the beneficial effects and molecular mechanism of YKGT and Ex using high fat diet induced MetS of C57BL/6 mice.

Methods

Catechins and caffeine in water extract of YKGT were measured via high performance liquid chromatography (HPLC). 10-week old mice were fed with high fat diet (HFD) for 10 weeks to induce obese mice. Then the obese mice were fed with continuous high fat diet (HFD), HFD with YKGT, HFD with Ex, and HFD with both YKGT and Ex for 8 weeks, respectively. The another group of 10-week old mice fed with low fat diet (LFD) were used as control.

Results

HPLC data revealed that YKGT has abundantly high concentration of epigallocatechin gallate (EGCG) and caffeine compared to Longjing 43 (Camellia sinensis var. sinensis) green tea. YKGT and Ex significantly decreased the level of blood glucose, serum total cholesterol (TC), triglyceride (TG), insulin, and alanine aminotransferase activity (ALT) when compared to HFD group. The fatty liver and hepatic pro-inflammatory gene expression in the YKGT, Ex and YKGT+Ex groups was mitigated significantly compared with HFD group, respectively. The phosphorylation of inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) and inhibitor of nuclear factor kappa-B α (IkBα) protein in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway was also decreased in YKGT or YKGT+Ex groups. The combination of YKGT and Ex prevented gene expression for lipid synthesis in the liver tissue, and significantly upregulated mRNA level of glucose transport genes in the skeletal muscles, when compared to the HFD group.

Conclusions

This study demonstrated that YKGT supplement or exercise appeared to reverse preexisting metabolic syndrome, and effectively relieved the fatty liver and hepatic inflammatory response induced by high fat diet. YKGT supplement and treadmill exercise together had better beneficial effects than only one intervention.
Diagnostic and severity scores for Cockayne syndrome
Authors: Spitz M. A. , Severac F. , Obringer C. , Baer S. , Le May N. , Calmels N. , Laugel V.
Published: February 2021

Background

Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. This rare condition encompasses a very wide spectrum of clinical severity levels ranging from severe prenatal onset to mild adult-onset subtypes. The rarity, complexity and variability of the disease make early diagnosis and severity assessment difficult. Based on similar approaches in other neurodegenerative disorders, we propose to validate diagnostic and severity scores for Cockayne syndrome.

Methods

Clinical, imaging and genetic data were retrospectively collected from 69 molecularly confirmed CS patients. A clinical diagnostic score and a clinical-radiological diagnostic score for CS were built using a multivariable logistic regression model with a stepwise variable selection procedure. A severity score for CS was designed on five items (head circumference, growth failure, neurosensorial signs, motor autonomy, communication skills) and validated by comparison with classical predefined severity subtypes of CS.

Results

Short stature, enophtalmos, hearing loss, cataracts, cutaneous photosensitivity, frequent dental caries, enamel hypoplasia, morphological abnormalities of the teeth, areflexia and spasticity were included in the clinical diagnostic score as being the most statistically relevant criteria. Appropriate weights and thresholds were assigned to obtain optimal sensitivity and specificity (95.7% and 86.4% respectively). The severity score was shown to be able to quantitatively differentiate classical predefined subtypes of CS and confirmed the continuous distribution of the clinical presentations in CS. Longitudinal follow-up of the severity score was able to reflect the natural course of the disease.

Conclusion

The diagnostic and severity scores for CS will facilitate early diagnosis and longitudinal evaluation of future therapeutic interventions. Prospective studies will be needed to confirm these findings.
Experiences of Australian podiatrists working through the 2020 coronavirus (COVID‐19) pandemic: an online survey
Authors: Williams Cylie M. , Couch Anna , Haines Terry , Menz Hylton B.
Published: February 2021

Background

On the 19th of January, 2020, the Chief Medical Officer of Australia issued a statement about a novel coronavirus, or SARS‐CoV‐2. Since this date, there have been variable jurisdictional responses, including lockdowns, and restrictions on podiatry practice. This study aimed to describe impacts of the SARS‐CoV‐2 pandemic on the podiatry profession in Australia.

Methods

This was a cross sectional study of Australian podiatrists using demographic data collected between 2017 and 2020, and pandemic‐related question responses collected between 30th March and 31st August, 2020. Data were collected online and participants described their work settings, patient funding types, business decisions and impacts, and information sources used to guide practice decisions during this time‐period. Inductive thematic analysis was used to analyse open‐ended questions about their practice impact of SARS‐CoV‐2.

Results

There were 732 survey responses, with 465 Australian podiatrists or podiatric surgeons providing responses describing pandemic impact. From these responses, 223 (49% of 453) podiatrists reported no supply issues, or having adequate supplies for the foreseeable future with personal protective equipment (PPE) or consumables to support effective infection prevention and control. The most frequent responses about employment, or hours of work, impact were reported in the various categories of “business as usual” (n = 312, 67%). Participants described most frequently using the local state and territory Department of Health websites (n = 347, 75%), and the Australian Podiatry Association (n = 334, 72%) to make decisions about their business. Overarching themes which resounded through open‐ended comments was that working through the pandemic was likened to a marathon, and not a sprint. Themes were: (i) commitment to do this, (ii) it's all in the plan, but not everything goes to plan, (iii) my support team must be part of getting through it, (iv) road blocks happen, and (v) nothing is easy, what's next?

Conclusion

Podiatrists in Australia reported variable pandemic impact on their business decisions, PPE stores, and their valued sources of information. Podiatrists also described their “marathon” journey through the pandemic to date, with quotes describing their challenges and highlights. Describing these experiences should provide key learnings for future workforce challenges, should further restrictions come into place.
Is polycystic ovary syndrome appropriately diagnosed by obstetricians and gynaecologists across China: a nationwide survey
Authors: Yan Deng , Yan-Fang Wang , Shi-Yang Zhu , Rui-Lin Ma , Xue-Song Ding , Xiao Ma , Wei Xue , Aijun Sun
Published: February 2021

Background

To describe the diagnostic criteria used and their application accuracy in the practice of polycystic ovary syndrome (PCOS) caring among obstetricians and gynaecologists across China.

Methods

This was an Online cross-sectional survey of Obstetricians and gynecologists involved in PCOS caring conducted via the largest continuing education platform of obstetrics and gynecology across China from September 2019 to November 2019.

Results

A total of 2,328 respondents were eligible for the final analysis. Of these, 94.5 % were general obstetricians and gynaecologists (Ge-ObGyn), and 5.5 % were reproductive endocrinologists (Re-ObGyn). Overall, the most frequently used criteria were the Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS) criteria (48.2 %), followed by the Rotterdam criteria (35.7 %) and NIH criteria (12.1 %). Of the respondents, 31.3 % used their diagnostic criteria in their clinical practice. More respondents who chose the Rotterdam criteria could accurately apply the diagnostic criteria than those who chose the AE-PCOS criteria (41.2 % vs. 32.1 %, P < 0.001). Compared with Ge-ObGyn, Re-ObGyn were less likely to use the AE-PCOS criteria (adjusted odds ratio, 0.513; 95 % CI, 0.328–0.802; P < 0.05) and 1.492 times more likely to accurately use their criteria (95 % CI, 1.014–2.196; P < 0.05).

Conclusions

Less than one-third of obstetricians and gynaecologists across China could accurately use the diagnostic criteria they choose to diagnose PCOS. There is an urgent need to train obstetricians and gynaecologists on PCOS diagnosis in an effort to improve the medical care quality of patients with PCOS.
Modeling schistosomiasis transmission: the importance of snail population structure
Authors: Anderson Larissa C. , Loker Eric S. , Wearing Helen J.
Published: February 2021

Background

Schistosomiasis is a neglected tropical disease endemic in 54 countries. A majorSchistosomaspecies,Schistosoma mansoni, is sustained via a life cycle that includes both human and snail hosts. Mathematical models ofS. mansonitransmission, used to elucidate the complexities of the transmission cycle and estimate the impact of intervention efforts, often focus primarily on the human host. However,S. mansoniincurs physiological costs in snails that vary with the age of the snail when first infected. Snail demography and the age of snail infection could thus affect the force of infection experienced by humans, which is frequently used to predict the impact of various control strategies.

Methods

To address how these snail host and parasite interactions influence model predictions, we developed deterministic models of schistosomiasis transmission that include varying complexity in the snail population age structure. Specifically, we examined how model outputs, such as schistosome prevalence in human and snail populations, respond to the inclusion of snail age structure.

Results

Our models suggest that snail population age structure modifies the force of infection experienced by humans and the relationship between snail infection prevalence and corresponding human infection prevalence. There are significant differences in estimated snail infection, cercarial density and mean worm burden between models without snail population dynamics and those with snail populations, and between models with a homogeneous snail population and those with age stratification. The variation between finely age-stratified snail populations and those grouped into only juvenile and adult life stages is, however, minimal.

Conclusions

These results indicate that including snails and snail age structure in a schistosomiasis transmission model alters the relationship between snail and human infection prevalence. This highlights the importance of accounting for a heterogeneous intermediate host population in models of schistosomiasis transmission where the impact of proposed control measures is being considered.

Graphical Abstract
Improved prediction of fracture risk leveraging a genome-wide polygenic risk score
Authors: Lu Tianyuan , Forgetta Vincenzo , Keller-Baruch Julyan , Nethander Maria , Bennett Derrick , Forest Marie , Bhatnagar Sahir , Walters Robin G. , Lin Kuang , Chen Zhengming , Li Liming , Karlsson Magnus , Mellström Dan , Orwoll Eric , McCloskey Eugene V. , Kanis John A. , Leslie William D. , Clarke Robert J. , Ohlsson Claes , Greenwood Celia M. T. , Richards J. Brent
Published: February 2021

Background

Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction.

Methods

We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors.

Results

A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072.

Conclusions

We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress
Authors: Bourebaba Lynda , Kornicka-Garbowska Katarzyna , Al Naem Mohamad , Röcken Michael , Łyczko Jacek , Marycz Krzysztof
Published: February 2021

Background

Protein tyrosine phosphatase 1B (PTP1B) is one of the major negative regulators of leptin and insulin signaling, and has been strongly implicated in insulin resistance development in the course of obesity and metabolic syndrome conditions; however, its exact role in controlling adipose tissue biogenesis is still poorly understood.

Objectives

This investigation aimed to elucidate whether selective inhibition of PTP1B using MSI-1436 compound may improve and restore the defective adipogenicity of ASCs isolated from EMS-affected horses.

Methods

Equine ASC EMS cells were cultured under adipogenic conditions in the presence of PTP1B inhibitor and were subsequently tested for expression of the main adipogenic-related genes using RT-qPCR, changes in free fatty acid profiles by means of GC-MS technique, and for mitochondrial dynamics improvement through the analysis of mitochondrial transmembrane potential and oxidative stress.

Results

Selective inhibition of PTP1B in equine ASC EMS cells improved substantially adipogenic differentiation by promoting cellular proliferation and normalizing expression of C/EBPalpha, PPARγ, and Adipoq markers that are critical for proper adipogenesis. Levels of secreted adiponectin and PPARγ were also shown to be increased in MSI-1436-conditioned cells, while total leptin levels markedly dropped under the same conditions. Moreover, MSI-1436 treatment enabled the regulation of metabolic-related transcripts that are crosslink to adipogenesis, namely Akt1, Akt2, and SHBG. The obtained results demonstrated also an obvious reduction in intracellular accumulated ROS and NO, as well as mitigated ER stress through the downregulation of Chop, Perk, Atf6, Ire1, and Xbp1 transcripts upon PTP1B inhibition. Furthermore, general fluctuations in FFA composition of all differentiated groups have been highlighted, where palmitic acid, palmitoleic acid, stearic acid, and linolelaidic acid that are known to be associated with the development of metabolic disorders were found to be normalized upon PTP1B inhibition during adipogenic differentiation.

Conclusion

The presented data provides the evidence that the use of PTP1B inhibitor may be successful in controlling and enhancing adipogenic differentiation of impaired equine ASCs affected by metabolic syndrome, and thus offers new insights for the management of obesity through the regulation of adipose tissue dynamics.

Graphical abstract
Low noise moving target detection in high resolution radar using binary codes
Authors: Alotaibi Majid
Published: February 2021

Radar technology plays a vital role in enhancing surveillance of the battlefields and physical borders, disease detection, and weather prediction. However, there exist certain challenges like detecting fast-moving targets. When targets are moving at a significantly high speed, it is not easy to detect them compared to static and slow-moving targets, which are easily detected. In this regard, the research community has, over the years, tried to improve radar technology to detect fast moving targets in presence of Doppler noise. In this paper, various binary codes have been proposed to minimize the noise peaks below the radar threshold limit to create multiple windows that enable precise information of the moving targets. These sequences also have good autocorrelation attributes to get a higher range resolution and compression ratio. Validation of the proposed method is performed using Matlab simulations. Results show that the noise amplitudes are reduced to 0.2 dB well below the prescribed threshold.
Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol
Authors: Eager Michael M. , Nolan Grant S. , Tonks Kathryn , Ramjeeawon Anoopama , Taylor Natalie
Published: February 2021

Background

More than 75% of patients presenting to the Emergency Department are suffering symptoms of pain. Despite this, 67% will not receive any analgesia. Methoxyflurane is a fluorinated hydrocarbon gas which has analgesic properties when inhaled. Penthrox is a methoxyflurane autoinhaler recently licenced in Europe. Its ease of administration, safety, and fast onset of action make it of particular relevance to emergency medicine. Additionally, outside the hospital, it has the advantage of increased temperature stability and portability over current standard care. New evidence of its efficacy is emerging; however, currently, its use in Europe is not widespread. The objective of this study will be to systematically evaluate the evidence on inhaled methoxyflurane to determine if it is a superior analgesia in the acute trauma setting.

Methods

We designed and registered a study protocol for a systematic review and meta-analysis on randomised controlled trials, comparing inhaled methoxyflurane and either placebo or standard care. A comprehensive search will be conducted from database inception onwards in MEDLINE, Embase, and the Cochrane CENTRAL database, concurrent with a search of the grey literature for other relevant studies, including clinical trial databases. Only randomised controlled trials will be included. No limitations will be imposed on publication status or language of publication. The primary outcome will be mean difference in patient-reported pain at time points within the first 30 min of administration. Secondary outcomes will be mean difference in time to clinically significant pain relief and relative risk of adverse effects. Two reviewers will independently screen all returned studies and collect data. Disagreements will be resolved through discussion or referral to a third reviewer. Individual study methodological quality will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis; if this is not possible, we will construct a narrative synthesis.

Discussion

This systematic review will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting. This knowledge will directly impact emergency care in the UK and worldwide and may require amendments to European pain relief guidelines.

Systematic review registration

PROSPERO CRD42020189119.
Effects of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial prevalence and prescribing in a tertiary hospital in Singapore
Authors: Ng Tat Ming , Tan Sock Hoon , Heng Shi Thong , Tay Hui Lin , Yap Min Yi , Chua Boon Hou , Teng Christine B. , Lye David C. , Lee Tau Hong
Published: February 2021

Background

The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing.

Methods

One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017–2019.

Results

The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p = 0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p < 0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p = 0.08).

Conclusion

During the COVID-19 pandemic, there was no increase in antimicrobial prescribing and no significant differences in antimicrobial prescribing quality indicators.
A simple one-step electrochemical deposition of bioinspired nanocomposite for the non-enzymatic detection of dopamine
Authors: Kathiresan Vijayaraj , Thirumalai Dinakaran , Rajarathinam Thenmozhi , Yeom Miri , Lee Jaewon , Kim Suhkmann , Yoon Jang-Hee , Chang Seung-Cheol
Published: February 2021

A simple and cost-effective electrochemical synthesis of carbon-based nanomaterials for electrochemical biosensor is of great challenge these days. Our study describes a single-step electrochemical deposition strategy to prepare a nanocomposite of electrochemically reduced graphene oxide (ErGO), multi-walled carbon nanotubes (MWCNTs), and polypyrrole (PPy) in an aqueous solution of pH 7.0 for dopamine (DA) detection. The ErGO/MWCNTs/PPy nanocomposites show enhanced electrochemical performance due to the strong π–π* stacking interactions among ErGO, MWCNTs, and PPy. The efficient interaction of the nanocomposites is confirmed by evaluating its physical and electrochemical characteristics using field-emission scanning electron microscopy, Raman spectroscopy, electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry. The deposited nanocomposites are highly stable on the substrates and possess high surface areas, which is vital to improve the sensitivity and selectivity for DA detection. The controlled deposition of the ErGO/MWCNTs/PPy nanocomposites can provide enhanced electrochemical detection of DA. The sensor demonstrates a short time response within 2 s and is a highly sensitive approach for DA detection with a dynamic linear range of 25–1000 nM (R2 = 0.999). The detection limit is estimated to be 2.3 nM, and the sensor sensitivity is calculated to be 8.96 μA μM−1 cm−2, with no distinct responses observed for other biological molecules.
Development of rapid advice guideline and standard and continuous updating guideline: experiences and practice
Authors: Jin Ying-Hui , Yao Xiao-Mei , Zeng Xian-Tao
Published: February 2021

We published rapid advice guidelines and updated guidelines for coronavirus disease 2019 (COVID-19) management on February 6, 2020, and September 4, 2020, respectively. These two guidelines vary widely in their developmental background, type of evidence, grade of recommendation and so on. We shared our experience for the development of these two guidelines to help clinical practitioners better understand and implement guidelines and to help guideline developers facilitate communication and discussion for guideline development during the pandemic.
A qualitative exploration of the patient experience of erosive and non-erosive hand osteoarthritis
Authors: Panter Charlotte , Berry Pamela , Chauhan Deven , Fernandes Sofia , Gatsi Sally , Park Josephine , Wells Jane R. , Arbuckle Rob
Published: February 2021

Background

Many patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA.

Methods

Thirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated.

Results

Most participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ.

Conclusions

This study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.
Hairless canary seeds (Phalaris canariensis L.) as a potential source of antioxidant, antihypertensive, antidiabetic, and antiobesity biopeptides
Authors: Urbizo-Reyes U. C. , Aguilar-Toalá J. E. , Liceaga A. M.
Published: February 2021

Rising consumer concerns with synthetic drugs to treat non-communicable diseases (NCDs) have promoted a shift towards using natural biological active constituents that offer similar health benefits. Hairless canary seed (Phalaris canariensis L) is an emerging crop traditionally used in Mexico to treat NCDs. Peptides liberated during simulated digestion of canary seed protein are believed to be responsible for their biological activity; however, no studies have shown the effect of controlled protein hydrolysis using commercial proteases on canary seed protein’s biological activity. Therefore, this study aimed to explore the in vitro antihypertensive, antidiabetic, and anti-obesity activity of canary seed peptides derived from proteolysis with Alcalase®. Protein fractions were primarily composed of prolamins (54.07 ± 1.8%), glutelins (32.19 ± 3.18%), globulins (5.97 ± 0.52%) and albumins (5.97 ± 0.52%). The < 3 kDa and 3–10 kDa peptide fractions showed the highest inhibition capacity (p< 0.05) towards angiotensin-converting enzyme (IC50= 0.028–0.032 mg/mL) lipase (IC50= 2.15–2.27 mg/mL), α-glucosidase (IC50= 0.82–1.15 mg/mL), and dipeptidyl-peptidase-IV (IC50= 1.27–1.60 mg/mL). Additionally, these peptide fractions showed high antioxidant activity against DPPH (134.22–150.66 μmol TE/mg) and ABTS (520.92–813.33 μmol TE/mg). These results provide an insight into the potential development of functional foods using commercial enzymatic hydrolysis of canary seed proteins for treating hypertension, type-2 diabetes, and obesity.
Chemotherapy Remote Care Monitoring Program: Integration of SMS Text Patient-Reported Outcomes in the Electronic Health Record and Pharmacist Intervention for Chemotherapy-Induced Nausea and Vomiting
Authors: Hough Shannon , McDevitt Rachel , Nachar Victoria R. , Kraft Shawna , Brown Anna , Christen Catherine , Frame David , Smerage Jeffrey B.
Published: February 2021

PURPOSE:

Chemotherapy-induced nausea and vomiting (CINV) is a common cause of unplanned healthcare utilization. The University of Michigan Rogel Cancer Center initiated the chemotherapy remote care monitoring program (CRCMP) to proactively identify patients experiencing CINV and intervene before the need for urgent evaluation.

METHODS:

High-risk patients for CINV are identified by neurokinin-1 (NK-1) antagonist administration, enrolled in the CRCMP, and received a daily text message survey for 7 days after chemotherapy administration to report symptoms. Responses above a set threshold trigger a message to the team pharmacist for intervention. The primary outcome of 14-day unplanned healthcare use was evaluated before and after CRCMP implementation.

RESULTS:

In 8 months, 652 patients received an NK-1 antagonist (2,244 cycles) and 387 patients were enrolled in the CRCMP (59%). Text message response rate was 94%. Clinical pharmacists provided 248 interventions in 121 patient episodes meeting threshold criteria. Fourteen-day unplanned healthcare use was decreased in the CRCMP-enrolled NK-1 episodes (6.68% v 4.53%, P = .02). Admissions were numerically lower for those enrolling in CRCMP when only admissions for nausea were considered (0.63% v 0.35%, P = .33).

CONCLUSION:

The CRCMP allowed for real-time management of patient-reported CINV symptom burden based on patient-reported outcomes (PROs) and an electronic medical record-integrated SMS text questionnaire. Clinical pharmacists were key team members to manage patient symptoms. Enrollment in CRCMP significantly reduced overall unplanned healthcare utilization. Although these changes were numerically small, any reduction in unnecessary care utilizing PROs can contribute to high-value care for patients with cancer.