bluuebunny/crossref_metadata_2025 huggingface dataset:
The first 30 years of the story of the Journal of Human Systems
Authors: Stratton Peter , Hanks Helga
Published: May 2021

We are writing this story of Human Systems with excitement and an eye to the future. Rudi Dallas and Becky Stancer took on the editing of the Journal but also joined with Peter Stratton and Helga Hanks in looking for a new base for the Journal. They succeeded in having Sage Publications include the Journal in their publications in internet form with Rudi Dallas and Becky Stancer as editors. This is a fantastic new beginning, in a contemporary format and with a new orientation of Therapy, Culture and Attachment. Peter Stratton and Helga Hanks have undertaken to give context to this new beginning by writing about the previous thirty-year history of Human Systems.
Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study
Authors: Morice Alyn , Smith Jaclyn A. , McGarvey Lorcan , Birring Surinder S. , Parker Sean M. , Turner Alice , Hummel Thomas , Gashaw Isabella , Fels Lueder , Klein Stefan , Francke Klaus , Friedrich Christian
Published: May 2021

Background

ATP actingviaP2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 receptor antagonist, in adults with RCC attending specialist centres.

Methods

In period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 1 week per dose level. Patients were randomised 1:1 to period A–B (n=20) or B–A (n=20). The primary efficacy end-point was change in cough frequency assessed over 24 h. The primary safety end-point was frequency and severity of adverse events (AEs).

Results

37 patients completed randomised therapy. Mean cough frequency fell by 17.4%versusbaseline with placebo. Eliapixant reduced cough frequency at doses ≥50 mg (reductionversusplacebo at 750 mg: 25% (90% CI 11.5–36.5%); p=0.002). Doses ≥50 mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41–49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5–21% with eliapixant; all were mild.

Conclusions

Selective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.
Long-term air pollution and road traffic noise exposure and COPD: the Danish Nurse Cohort
Authors: Liu Shuo , Lim Youn-Hee , Pedersen Marie , Jørgensen Jeanette T. , Amini Heresh , Cole-Hunter Thomas , Mehta Amar J. , So Rina , Mortensen Laust H. , Westendorp Rudi G.J. , Loft Steffen , Bräuner Elvira V. , Ketzel Matthias , Hertel Ole , Brandt Jørgen , Jensen Steen S. , Christensen Jesper H. , Sigsgaard Torben , Geels Camilla , Frohn Lise M. , Brboric´ Maja , Radonic´ Jelena , Turk Sekulic Maja , Bønnelykke Klaus , Backalarz Claus , Simonsen Mette K. , Andersen Zorana J.
Published: May 2021

Background

While air pollution has been linked to the development of chronic obstructive pulmonary disease (COPD), evidence on the role of environmental noise is just emerging. We examined the associations of long-term exposure to air pollution and road traffic noise with COPD incidence.

Methods

We defined COPD incidence for 24 538 female nurses from the Danish Nurse Cohort (age >44 years) as the first hospital contact between baseline (1993 or 1999) and 2015. We estimated residential annual mean concentrations of particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) since 1990 and nitrogen dioxide (NO2) since 1970 using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System modelling system, and road traffic noise (Lden) since 1970 using the Nord2000 model. Time-varying Cox regression models were applied to assess the associations of air pollution and road traffic noise with COPD incidence.

Results

977 nurses developed COPD during a mean of 18.6 years’ follow-up. We observed associations with COPD for all three exposures with HRs and 95% CIs of 1.19 (1.01–1.41) per 6.26 µg·m−3for PM2.5, 1.13 (1.05–1.20) per 8.19 µg·m−3for NO2and 1.15 (1.06–1.25) per 10 dB for Lden. Associations with NO2and Ldenattenuated slightly after mutual adjustment, but were robust to adjustment for PM2.5. Associations with PM2.5were attenuated to null after adjustment for either NO2or Lden. No potential interaction effect was observed between air pollutants and noise.

Conclusion

Long-term exposure to air pollution, especially traffic-related NO2, and to road traffic noise were independently associated with COPD.
Compatibility of a novel filter paper-based bio-safe sputum transport kit with line probe assay for diagnosing drug-resistant tuberculosis: a single-site evaluation study
Authors: Anthwal Divya , Gupta Rakesh Kumar , Singhal Ritu , Bhalla Manpreet , Verma Ajoy Kumar , Khayyam Khalid Umar , Myneedu Vithal Prasad , Sarin Rohit , Gupta Ashawant , Gupta Nalini Kant , Singh Manjula , Sivaswami Tyagi Jaya , Haldar Sagarika
Published: May 2021

Background

Near-patient access to appropriate tests is a major obstacle for the efficient diagnosis of tuberculosis (TB) and associated drug resistance.

Methods

We recently developed the “TB Concentration & Transport” kit for bio-safe, ambient-temperature transportation of dried sputum onTrans-Filter, and the “TB DNA Extraction” kit for DNA extraction fromTrans-Filter for determining drug resistance by DNA sequencing. In the present study, we evaluated the compatibility of Kit-extracted DNA with Hain's line probe assays (LPAs), which are endorsed by National TB programmes for the detection of drug resistance in sputum collected from presumptive multidrug-resistant TB patients (n=207).

Results

Trans-Filter-extracted DNA was seamlessly integrated with the LPA protocol (Kit-LPA). The sensitivity of Kit-LPA for determining drug resistance was 83.3% for rifampicin (95% CI 52–98%), 77.7% for isoniazid (95% CI 52–94%), 85.7% for fluoroquinolones (95% CI 42–100%) and 66.6% for aminoglycosides (95% CI 9–99%), with a specificity range of 93.7% (95% CI 87–97) to 99.1% (95% CI 95–100) using phenotypic drug susceptibility testing (DST) as a reference standard. A high degree of concordance was noted between results obtained from Kit-LPA and LPA (99% to 100% (κ value: 0.83–1.0)).

Conclusions

This study demonstrates successful integration of our developed kits with LPA. The adoption of these kits across Designated Microscopy Centres in India can potentially overcome the existing challenge of transporting infectious sputum at controlled temperature to centralised testing laboratories and can provide rapid near-patient cost-effective “Universal DST” services to TB subjects residing in remote areas.
Quantitative18F-fluorodeoxyglucose positron emission tomography/computed tomography to assess pulmonary inflammation in COPD
Authors: Vass Laurence , Fisk Marie , Cheriyan Joseph , Mohan Divya , Forman Julia , Oseni Adelola , Devaraj Anand , Mäki-Petäjä Kaisa M. , McEniery Carmel M. , Fuld Jonathan , Hopkinson Nicholas S. , Lomas David A. , Cockcroft John R. , Tal-Singer Ruth , Polkey Michael I. , Wilkinson Ian B.
Published: May 2021

Rationale

COPD and smoking are characterised by pulmonary inflammation.18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker.

Objectives

To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in “usual” (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients.

Methods

Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKiand systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKivalues at baseline and at 4-month follow-up.

Results

COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001versus0.0028±0.001 mL·cm−3·min−1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi(β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKibetween the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%.

Conclusions

FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.
Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes
Authors: Fujii Wataru , Kapellos Theodore S. , Baßler Kevin , Händler Kristian , Holsten Lisa , Knoll Rainer , Warnat-Herresthal Stefanie , Oestreich Marie , Hinkley Emily R. , Hasenauer Jan , Pizarro Carmen , Thiele Christoph , Aschenbrenner Anna C. , Ulas Thomas , Skowasch Dirk , Schultze Joachim L.
Published: May 2021

Background

Immune cells play a major role in the pathogenesis of COPD. Changes in the distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils are well known; however, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood.

Method

To determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin−HLA-DR+CD66b−AutofluorescencehiAMs from controls and COPD patients.

Results

We observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner.

Conclusions

Transcriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon-α and γ responses.
In Situ Fabrication of Activated Carbon from a Bio-Waste Desmostachya bipinnata for the Improved Supercapacitor Performance
Authors: Gupta Gopal Krishna , Sagar Pinky , Pandey Sumit Kumar , Srivastava Monika , Singh A. K. , Singh Jai , Srivastava Anchal , Srivastava S. K. , Srivastava Amit
Published: May 2021

Herein, we demonstrate the fabrication of highly capacitive activated carbon (AC) using a bio-waste Kusha grass (Desmostachya bipinnata), by employing a chemical process followed by activation through KOH. The as-synthesized few-layered activated carbon has been confirmed through X-ray powder diffraction, transmission electron microscopy, and Raman spectroscopy techniques. The chemical environment of the as-prepared sample has been accessed through FTIR and UV–visible spectroscopy. The surface area and porosity of the as-synthesized material have been accessed through the Brunauer–Emmett–Teller method. All the electrochemical measurements have been performed through cyclic voltammetry and galvanometric charging/discharging (GCD) method, but primarily, we focus on GCD due to the accuracy of the technique. Moreover, the as-synthesized AC material shows a maximum specific capacitance as 218 F g−1 in the potential window ranging from − 0.35 to + 0.45 V. Also, the AC exhibits an excellent energy density of ~ 19.3 Wh kg−1 and power density of ~ 277.92 W kg−1, respectively, in the same operating potential window. It has also shown very good capacitance retention capability even after 5000th cycles. The fabricated supercapacitor shows a good energy density and power density, respectively, and good retention in capacitance at remarkably higher charging/discharging rates with excellent cycling stability. Henceforth, bio-waste Kusha grass-derived activated carbon (DP-AC) shows good promise and can be applied in supercapacitor applications due to its outstanding electrochemical properties. Herein, we envision that our results illustrate a simple and innovative approach to synthesize a bio-waste Kusha grass-derived activated carbon (DP-AC) as an emerging supercapacitor electrode material and widen its practical application in electrochemical energy storage fields.
“Old wine in a new bottle” - post COVID-19 infection, central serous chorioretinopathy and the steroids
Authors: Sanjay Srinivasan , Gowda Poornachandra B. , Rao Bhimasena , Mutalik Deepashri , Mahendradas Padmamalini , Kawali Ankush , Shetty Rohit
Published: May 2021

Introduction

Corona virus disease (COVID-19) pandemic can cause myriad of ocular manifestations.

We report a case of unilateral multi focal central serous retinopathy, post COVID-19 infection in an Asian Indian female.

Case presentation

A 42-year-old female presented to us with unilateral blurring, in the right eye (OD), 12 days after COVID-19 infection. She had fever, chills, shortness of breath and cough with tiredness and was COVID- RT PCR positive. She was administered intravenous and oral antibiotics with injection heparin/remdesivir, during her 7 day stay at the hospital. She was also on steroid inhalers. She had no systemic history of note.

On ocular evaluation, her corrected distance visual acuity was 20/40 in OD and 20/20 in left eye (OS). Anterior segment was normal. Anterior vitreous was clear. Fundus examination of the OD showed central serous retinopathy (CSCR) with OS being normal.

Conclusion

CSCR can occur post COVID-19 due to steroid administration and physicians administering it should be aware of this and refer the patients to an ophthalmologist earlier.
A novel essential protein identification method based on PPI networks and gene expression data
Authors: Zhong Jiancheng , Tang Chao , Peng Wei , Xie Minzhu , Sun Yusui , Tang Qiang , Xiao Qiu , Yang Jiahong
Published: May 2021

Background

Some proposed methods for identifying essential proteins have better results by using biological information. Gene expression data is generally used to identify essential proteins. However, gene expression data is prone to fluctuations, which may affect the accuracy of essential protein identification. Therefore, we propose an essential protein identification method based on gene expression and the PPI network data to calculate the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network. Our experiments show that the method can improve the accuracy in predicting essential proteins.

Results

In this paper, we propose a new measure named JDC, which is based on the PPI network data and gene expression data. The JDC method offers a dynamic threshold method to binarize gene expression data. After that, it combines the degree centrality and Jaccard similarity index to calculate the JDC score for each protein in the PPI network. We benchmark the JDC method on four organisms respectively, and evaluate our method by using ROC analysis, modular analysis, jackknife analysis, overlapping analysis, top analysis, and accuracy analysis. The results show that the performance of JDC is better than DC, IC, EC, SC, BC, CC, NC, PeC, and WDC. We compare JDC with both NF-PIN and TS-PIN methods, which predict essential proteins through active PPI networks constructed from dynamic gene expression.

Conclusions

We demonstrate that the new centrality measure, JDC, is more efficient than state-of-the-art prediction methods with same input. The main ideas behind JDC are as follows: (1) Essential proteins are generally densely connected clusters in the PPI network. (2) Binarizing gene expression data can screen out fluctuations in gene expression profiles. (3) The essentiality of the protein depends on the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network.
Metabolome and transcriptome analysis reveals the molecular profiles underlying the ginseng response to rusty root symptoms
Authors: Bian Xingbo , Zhao Yan , Xiao Shengyuan , Yang He , Han Yongzhong , Zhang Lianxue
Published: May 2021

Background

Ginseng rusty root symptoms (GRS) is one of the primary diseases of ginseng. This disease leads to a severe decline in the quality of ginseng. It has been shown that the occurrence of GRS is associated with soil environmental degradation, which may involve changes in soil microbiology and physicochemical properties.

Results

In this study, GRS and healthy ginseng (HG) samples were used as experimental materials for comparative analysis of transcriptome and metabolome. Compared with those in HG samples, 949 metabolites and 9451 genes were significantly changed at the metabolic and transcriptional levels in diseased samples. The diseased tissues’ metabolic patterns changed, and the accumulation of various organic acids, alkaloids, alcohols and phenols in diseased tissues increased significantly. There were significant differences in the expression of genes involved in plant hormone signal transduction, phenylpropanoid biosynthesis, the peroxidase pathway, and the plant-pathogen interaction pathway.

Conclusion

The current study involved a comparative metabolome and transcriptome analysis of GRS and HG samples. Based on the findings at the transcriptional and metabolic levels, a mechanism model of the ginseng response to GRS was established. Our results provide new insights into ginseng’s response to GRS, which will reveal the potential molecular mechanisms of this disease in ginseng.
Exploring polypharmacy burden among elderly patients with chronic diseases in Chinese community: a cross-sectional study
Authors: Wang Yongli , Li Xiaodan , Jia Dongmei , Lin Beilei , Fu Bo , Qi Bei , Zhang Zhenxiang
Published: May 2021

Background

In the long-term use of multiple medications for elderly patients diagnosed with chronic diseases, medication problems are prominent, which seriously reduces their quality of life. The burden of medications of patients critically affects their medication beliefs, behaviors and disease outcomes. It may be a solution to stress the burden of medications of patients. Its medication issues develops a novel perspective. The present study aimed to exploit the Chinese version of Living with Medicines Questionnaire-3(C-LMQ-3) to quantify the medicines burden of elderly patients diagnosed with chronic diseases in China, and evaluate the relevant demographic characteristics of sub-populations with high medicines burden.

Methods

The survey was distributed to elderly patients aged ≥ 60 years with chronic disease by using ≥ 5 medicines, C-LMQ-3 scores and domain scores were compared by the characteristics of elderly patients by employing descriptive statistics and performing statistical tests.

Results

On the whole, 430 responses were analyzed, and the participants were aged between 60 and 91 years, with the average age of 73.57 years (SD: 7.87). Most of the responses were female (61.7 %) with middle school education (38.5 %). Moreover, 54.1 % of the participants lived with spouse only, 16.2 % had both spouse and children, and 10.0 % lived alone. As indicated from regression analysis, higher C-LMQ-3 scores were associated with those who were with low education level, 60–69 years-old, using ≥ 11 medicines, using medicines ≥ 3 times a day, income per month (RMB) ≤ 3000, and who having higher monthly self-paid medication (RMB) ≥ 300 (p < 0.01). Burden was mainly driven by cost-related burden, concerns about medicines, and the lack of autonomy over medicine regimens.

Conclusions

This study presents the preliminary evidence to elderly patients diagnosed with chronic diseases in mainland China that pay attention to multiple medications burden may help reduce the Drug Related Problems, whereas some elderly patients have a higher burden of medication. Chinese health care providers are required to primarily evaluate and highlight such patients, and formulate relevant intervention strategies to ensure medication adherence and daily medication management of elderly patients with polypharmacy.
A nomogram incorporating functional and tubular damage biomarkers to predict the risk of acute kidney injury for septic patients
Authors: Ma Jianchao , Deng Yujun , Lao Haiyan , Ouyang Xin , Liang Silin , Wang Yifan , Yao Fen , Deng Yiyu , Chen Chunbo
Published: May 2021

Background

Combining tubular damage and functional biomarkers may improve prediction precision of acute kidney injury (AKI). Serum cystatin C (sCysC) represents functional damage of kidney, while urinary N-acetyl-β-D-glucosaminidase (uNAG) is considered as a tubular damage biomarker. So far, there is no nomogram containing this combination to predict AKI in septic cohort. We aimed to compare the performance of AKI prediction models with or without incorporating these two biomarkers and develop an effective nomogram for septic patients in intensive care unit (ICU).

Methods

This was a prospective study conducted in the mixed medical-surgical ICU of a tertiary care hospital. Adults with sepsis were enrolled. The patients were divided into development and validation cohorts in chronological order of ICU admission. A logistic regression model for AKI prediction was first constructed in the development cohort. The contribution of the biomarkers (sCysC, uNAG) to this model for AKI prediction was assessed with the area under the receiver operator characteristic curve (AUC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). Then nomogram was established based on the model with the best performance. This nomogram was validated in the validation cohort in terms of discrimination and calibration. The decision curve analysis (DCA) was performed to evaluate the nomogram’s clinical utility.

Results

Of 358 enrolled patients, 232 were in the development cohort (69 AKI), while 126 in the validation cohort (52 AKI). The first clinical model included the APACHE II score, serum creatinine, and vasopressor used at ICU admission. Adding sCysC and uNAG to this model improved the AUC to 0.831. Furthermore, incorporating them significantly improved risk reclassification over the predictive model alone, with cNRI (0.575) and IDI (0.085). A nomogram was then established based on the new model including sCysC and uNAG. Application of this nomogram in the validation cohort yielded fair discrimination with an AUC of 0.784 and good calibration. The DCA revealed good clinical utility of this nomogram.

Conclusions

A nomogram that incorporates functional marker (sCysC) and tubular damage marker (uNAG), together with routine clinical factors may be a useful prognostic tool for individualized prediction of AKI in septic patients.
Utilization of growth monitoring and promotion is highest among children aged 0–11 months: a survey among mother-child pairs from rural northern Ghana
Authors: Seidu Fusheini , Mogre Victor , Yidana Adadow , Ziem Juventus B.
Published: May 2021

Background

More than half of all deaths in under 5 children is related to malnutrition. Child malnutrition could be prevented through regular monitoring of the growth and development of children and the implementation of growth promotion activities referred to as growth monitoring and promotion (GMP). Mothers’/caregivers utilization of these activities through child welfare clinics could improve the growth and development of under 5 children. We evaluated mothers’ knowledge on GMP, utilization and associated factors among mother-child pairs from a poor socio-economic district in Northern Ghana.

Methods

Using an analytical cross-sectional design, participants included mothers with children aged 0–59 months, grouped into 0–11 months, 12–23 months and 24–59 months. A semi-structured questionnaire containing both closed- and open-ended questions was used to collect data. Multivariate logistic regression was used to identify determinants of GMP utilization.

Results

Four hundred mother-child pairs were included in the study. Overall, 28.5% (n = 114) of the mothers utilized GMP services. Almost 60%(n = 237) of the mothers knew the recommended age to seek for GMP service for their children. Only 9% of the mothers could correctly interpret the directions of the growth curves in their children’s Health Record booklet. Mothers with children aged 0–11 months were 3.9 times more likely (p = 0.009) to utilize GMP services compared to their counterparts with children aged 12–23 months and 24–59 months. Mothers who had low level of knowledge were 2.19 times (p = 0.003) more likely to utilize GMP services compared to their counterparts with high level of knowledge..

Conclusion

Utilization of GMP services was low and particularly lower in children aged 24–59 months. Mothers’ knowledge in GMP was optimal although there were notable gaps.
Effects of maternal consumption of morphine on rat skeletal system development
Authors: Saeidinezhad Maryam , Razban Vahid , Safizadeh Hosein , Ezzatabadipour Massood
Published: May 2021

Background

Opioid abuse is among the most ubiquitous issues world-wide, and when it happens in mothers, it puts them at risk of diseases that can be transferred to the next generation. Previous studies have indicated that morphine addiction during pregnancy could inhibit development in rat embryos and infants.

The present study focused on the effects of maternal consumption of morphine on rat skeletal system development and also investigate the molecular pathway of chondrogenesis and osteogenesis of infants from control and addicted rat groups.

Methods

Thirty-two female rats were randomly assigned to four groups. The groups consisted of one- and seven-day-old female infants which were born of morphine-dependent mothers and a control group for each of them. Experimental groups received oral morphine at the final dose of 0.4 mg/ml/day. Withdrawal signs were confirmation of morphine dependency. Female rats were crossed with male rats and coupling time was recorded. Fixed bones of all groups were processed and then stained by hematoxyline-eosin method. Thickness and cell number of proximal and distal growth plate of bones were measured. The cartilage and bone cells were stained by alcian blue/alizarin red method. Additionally, the gene expression of alkaline phosphatase, osteocalcin, and COLL2 and SOX9 gene expression were studied immuno-histochemically.

Results

Unfavorable effects of morphine on histological measurements were observed in one-day and seven-day infants, with more effects on seven-day infants. The thickness and cell number of the proximal and distal growth plate of morphine-dependent rat offsprings were reduced significantly. Furthermore, morphine reduced growth of primary and secondary ossification centers, and thus, longitudinal bone growth was reduced. Moreover, a decrease in the alkaline phosphatase, osteocalcin, COLL2 and SOX9 gene expression, and the number of stained cells was observed. More adverse effects of morphine in seven-day infants compared to one-day infants which showed the time dependent of morphine to the time length of administration.

Conclusion

Histochemistry and immunohistochemistry findings on cartilage and bone matrix formation, as well as protein expression of chondrogenic and osteogenic markers suggest that morphine dependence in pregnant mothers may impair intra-cartilaginous osteogenesis in post-natal rats.
Value of passive anterior tibial subluxation on axial MRI in identifying anterior cruciate ligament functional deficiency in patients with advanced anteromedial osteoarthritis of the knee: a case-control study
Authors: Tao Yuzhang , Tang Siying , Zhao Pei , Yan Wenlong , Zhou Aiguo , Zhang Jian
Published: May 2021

Background

A functionally deficient anterior cruciate ligament (ACL) is considered one of the contraindications in unicompartmental knee arthroplasty (UKA). But there is still a lack of standardized and reproducible methods to assess ACL functional integrity in patients with advanced anteromedial osteoarthritis of the knee (AMOA). This study explores the value of passive anterior tibial subluxation (PATS) on axial MRI in evaluating ACL status in this population.

Methods

Patients who met UKA indications between November 2017 and September 2020 were included and grouped into “intact” (ACLI) or “deficient” (ACLD) group according to their ACL status during surgery. All participants underwent MRI with a standardized protocol. The measurements of medial and lateral PATS were conducted on axial MRI, and the mean of them was calculated as global PATS. Then the reliability and diagnostic ability of PATS were determined.

Results

A total of 85 patients (45 for ACLI group, 40 for ACLD group) were included after selection. The measurements of PATS showed excellent intra- and inter-observer reliabilities (with an intraclass correlation coefficient of at least 0.986). The global PATS of the ACLI group was significantly lower than that of the ACLD group (− 2.30 ± 1.96 vs. 1.03 ± 1.96 mm, P<0.0001). The diagnostic ability of global PATS was good (area under the curve = 0.897), and a threshold of 1.2 mm had a specificity of 100%, a sensitivity of 55%, and an accuracy of 78.82%.

Conclusion

An axial global PATS of 1.2 mm on MRI is greatly specific for identifying a functionally deficient ACL in patients with advanced AMOA.
Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis
Authors: Gregoriano Claudia , Damm Dominik , Kutz Alexander , Koch Daniel , Wolfisberg Selina , Haubitz Sebastian , Conen Anna , Bernasconi Luca , Hammerer-Lercher Angelika , Fux Christoph A. , Mueller Beat , Schuetz Philipp
Published: May 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19.

Methods

We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality.

Results

Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality.

Conclusions

Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.
Metabolic classification of bladder cancer based on multi-omics integrated analysis to predict patient prognosis and treatment response
Authors: Tang Chaozhi , Yu Meng , Ma Jiakang , Zhu Yuyan
Published: May 2021

Background

Currently, no molecular classification is established for bladder cancer based on metabolic characteristics. Therefore, we conducted a comprehensive analysis of bladder cancer metabolism-related genes using multiple publicly available datasets and aimed to identify subtypes according to distinctive metabolic characteristics.

Methods

RNA-sequencing data of The Cancer Genome Atlas were subjected to non-negative matrix fractionation to classify bladder cancer according to metabolism-related gene expression; Gene Expression Omnibus and ArrayExpress datasets were used as validation cohorts. The sensitivity of metabolic types to predicted immunotherapy and chemotherapy was assessed. Kaplan–Meier curves were plotted to assess patient survival. Differentially expressed genes between subtypes were identified using edgeR. The differences among identified subtypes were compared using the Kruskal–Wallis non-parametric test. To better clarify the subtypes of bladder cancer, their relationship with clinical characteristics was examined using the Fisher’s test. We also constructed a risk prediction model using the random survival forest method to analyze right-censored survival data based on key metabolic genes. To identify genes of prognostic significance, univariate Cox regression, lasso analysis, and multivariate regression were performed sequentially.

Results

Three bladder cancer subtypes were identified according to the expression of metabolism-related genes. The M1 subtype was characterized by high metabolic activity, low immunogenicity, and better prognosis. M2 exhibited moderate metabolic activity, high immunogenicity, and the worst prognosis. M3 was associated with low metabolic activity, low immunogenicity, and poor prognosis. M1 showed the best predicted response to immunotherapy, whereas patients with M1 were predicted to be the least sensitive to cisplatin. By contrast, M2 showed the worst predicted response to immunotherapy but was predicted to be more sensitive to cisplatin, doxorubicin, and other first-line anticancer drugs. M3 was the most sensitive to gemcitabine. The risk model based on metabolic genes effectively predicted the prognosis of bladder cancer patients.

Conclusions

Metabolic classification of bladder cancer has potential clinical value and therapeutic feasibility by inhibiting the associated pathways. This classification can provide valuable insights for developing precise bladder cancer treatment.
miR-155 and miR-146a collectively regulate meningitic Escherichia coli infection-mediated neuroinflammatory responses
Authors: Yang Bo , Yang Ruicheng , Xu Bojie , Fu Jiyang , Qu Xinyi , Li Liang , Dai Menghong , Tan Chen , Chen Huanchun , Wang Xiangru
Published: May 2021

Background

Escherichia coli is the most common Gram-negative bacterium causing meningitis, and E. coli meningitis is associated with high mortality and morbidity throughout the world. Our previous study showed that E. coli can colonize the brain and cause neuroinflammation. Increasing evidence supports the involvement of miRNAs as key regulators of neuroinflammation. However, it is not clear whether these molecules participate in the regulation of meningitic E. coli-mediated neuroinflammation.

Methods

The levels of miR-155 and miR-146a, as well as their precursors, in E. coli-infected astrocytes were measured using quantitative real-time PCR (qPCR). Overexpression and knockdown studies of miR-155 and miR-146a were performed to observe the effects on bacterial loads, cytokines, chemokines, and NF-κB signaling pathways. Bioinformatics methods were utilized to predict the target genes, and these target genes were validated using qPCR, Western blotting, and luciferase reporter system. In vivo knockdown of miR-155 and miR-146a was carried out to observe the effects on bacterial loads, inflammatory genes, astrocyte activation, microglia activation, and survival in a mouse model.

Results

The levels of miR-155, miR-146a, and their precursors were significantly increased in astrocytes during E. coli infection. miR-155 and miR-146a were induced by the NF-κB-p65 signaling pathway upon infection. Overexpressing and inhibiting miR-155 and miR-146a in astrocytes did not affect the bacterial loads. Further, the in vitro overexpression of miR-155 and miR-146a suppressed the E. coli-induced inflammatory response, whereas the inhibition of miR-155 and miR-146a enhanced it. Mechanistically, miR-155 inhibited TAB2, and miR-146a targeted IRAK1 and TRAF6; therefore, they functioned collaboratively to modulate TLR-mediated NF-κB signaling. In addition, both miR-155 and miR-146a could regulate the EGFR–NF-κB signaling pathway. Finally, the in vivo suppression of E. coli-induced miR-155 and miR-146a further promoted the production of inflammatory cytokines, aggravated astrocyte and microglia activation, and decreased mouse survival time, without affecting the bacterial loads in the blood and brain.

Conclusions

E. coli infection induced miR-155 and miR-146a, which collectively regulated bacteria-triggered neuroinflammatory responses through negative feedback regulation involving the TLR-mediated NF-κB and EGFR–NF-κB signaling pathways, thus protecting the central nervous system from further neuroinflammatory damage.
Beyond knowledge acquisition: factors influencing family planning utilization among women in conservative communities in Rural Burundi
Authors: Hakizimana Sonia , Odjidja Emmanuel Nene
Published: May 2021

Background

With a fertility rate of 5.4 children per woman, Burundi ranked as seventh country with the highest fertility rate in the world. Family planning is an effective way of achieving desirable family size, appropriate birth spacing and significant reduction in unintended pregnancies. Furthermore, family planning has been linked to improvements in maternal health outcomes. Yet, in spite of the overwhelming evidence on the benefits of family planning and despite high knowledge and free services, utilisation is low especially in rural communities with conservative people. Employing a mixed methods approach, this study first quantifies contraceptive prevalence and second, explores the contextual multilevel factors associated with low family planning utilisation among community members.

Methods

An explanatory sequential mixed study was conducted. Five hundred and thirty women in union were interviewed using structured and pre-tested questionnaire. Next, 11 focus group discussions were held with community members composed of married men and women, administrative and religious leaders (n = 132). The study was conducted in eighteen collines of two health districts of Vyanda and Rumonge in Bururi and Rumonge provinces in Burundi. Quantitative data was analysed with SPSS and qualitative data was coded and deductive thematic methods were applied to find themes and codes.

Results

The overall contraceptive prevalence was 22.6%. From logistic modelling analysis, it was found that women aged 25 to 29 (aOR 5.04 (95% CI 2.09–10.27 p = 0.038), those that have completed secondary school and having four or less children were significantly associated with use of family planning (aOR 1.72 (95%1.35–2.01) p = 0.002). Among factors why family planning was unused included experience with side effects and costs associated with its management in the health system. Religious conceptualisation and ancestral negative beliefs of family planning had also shaped how people perceived it. Furthermore, at the household level, gender imbalances between spouses had resulted in break in communication, also serving as a factor for non-use of family planning.

Conclusion

Given that use of family planning is rooted in negative beliefs emanating mainly from religious and cultural practices, engaging local religious leaders and community actors may trigger positive behaviours change needed to increase its use.
Risk factor analysis of pulmonary cement embolism during percutaneous vertebroplasty or kyphoplasty for osteoporotic vertebral compression fractures
Authors: Zou Dexin , Dong Shengjie , Du Wei , Sun Bing , Wu Xifa
Published: May 2021

Objective

The purpose of this research is to evaluate the risk factors and incidence of pulmonary cement embolism (PCE) during percutaneous vertebroplasty (PVP) or kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) based on postoperative computed tomography (CT).

Methods

A total of 2344 patients who underwent PVP or PKP due to OVCFs in our spine center were analyzed retrospectively. According to the detection of postoperative pulmonary CT, the patients were divided into two groups: pulmonary cement embolism group (PCE group) and non-pulmonary cement embolism group (NPCE group). Demographic data in both groups were compared using the χ2 test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was carried out to identify risk factors that were significantly related to the PCE resulting from cement leakage.

Results

PCE was found in 34 patients (1.9% 34/1782) with pulmonary CT examination after operation. There was no statistically significant difference in the parameters such as age, gender, body mass index (BMI), and cement volume in the two groups. Patients with three or more involved vertebrae had a significantly increased risk to suffer from PCE than those with one involved vertebra (p=0.046 OR 2.412 [95% CI 1.017–5.722]). Patients who suffered thoracic fracture had a significantly increased risk to suffer from PCE than those who suffered thoracolumbar fracture (p=0.001 OR 0.241 [95% CI 0.105–0.550]). And significantly increased PCE risk also was observed in thoracic fracture compared with lumbar fracture patients (p=0.028 OR 0.094 [95% CI 0.114–0.779]). The risk of PCE within 2 weeks after fracture was significantly higher than that after 2 weeks of fracture (p=0.000 OR 0.178 [95% CI 0.074–0.429]). Patients who underwent PVP surgery had a significantly increased PCE risk than those who underwent PKP surgery (p=0.001 OR 0.187 [95% CI 0.069–0.509]).

Conclusion

The real incidence of PCE is underestimated due to the lack of routine postoperative pulmonary imaging examination. The number of involved vertebrae, fracture location, operation timing, and operation methods are independent risk factors for PCE.
The impact of rarity in NICE’s health technology appraisals
Authors: Clarke Sophie , Ellis Michelle , Brownrigg Jack
Published: May 2021

Background

In the absence of a framework designed to evaluate medicines for rare diseases in the UK, most orphan medicines are appraised by the National Institute for Health and Care Excellence (NICE) through the Single Technology Appraisal (STA) process.

Results

An analysis of STA appraisals of orphan and non-orphan medicines revealed that orphan medicines were subject to a significantly longer mean time in the NICE process than non-orphan medicines [370 days (n = 44) vs. 277 days (n = 118), p =  < 0.0001]. A higher proportion of orphan STAs required more than one Appraisal Committee Meeting (ACM) versus non-orphan STAs, and orphan STAs were disadvantaged by worse outcomes with respect to positive recommendations than those orphan medicines assessed by Highly Specialised Technology evaluation (HST).

Conclusions

The uncertainties inherent to developing orphan medicines may contribute to these disadvantages. Improved understanding of the challenges in drug development for orphan medicines and clearer guidance for decision makers on navigating uncertainty in the HTA process may promote greater equity in access to medicines across rare and common conditions.
Effect of the transcription factor YY1 on the development of pancreatic endocrine and exocrine tumors: a narrative review
Authors: Chen Qun , Wang Wu-Jun , Jia Yun-Xuan , Yuan Hao , Wu Peng-Fei , Ge Wan-Li , Meng Ling-Dong , Huang Xu-Min , Shen Peng , Yang Tao-Yue , Miao Yi , Zhang Jing-Jing , Jiang Kui-Rong
Published: May 2021

Pancreatic tumors are classified into endocrine and exocrine types, and the clinical manifestations in patients are nonspecific. Most patients, especially those with pancreatic ductal adenocarcinoma (PDAC), have lost the opportunity to receive for the best treatment at the time of diagnosis. Although chemotherapy and radiotherapy have shown good therapeutic results in other tumors, their therapeutic effects on pancreatic tumors are minimal. A multifunctional transcription factor, Yin-Yang 1 (YY1) regulates the transcription of a variety of important genes and plays a significant role in diverse tumors. Studies have shown that targeting YY1 can improve the survival time of patients with tumors. In this review, we focused on the mechanism by which YY1 affects the occurrence and development of pancreatic tumors. We found that a YY1 mutation is specific for insulinomas and has a role in driving the degree of malignancy. In addition, changes in the circadian network are a key causative factor of PDAC. YY1 promotes pancreatic clock progression and induces malignant changes, but YY1 seems to act as a tumor suppressor in PDAC and affects many biological behaviors, such as proliferation, migration, apoptosis and metastasis. Our review summarizes the progress in understanding the role of YY1 in pancreatic endocrine and exocrine tumors and provides a reasonable assessment of the potential for therapeutic targeting of YY1 in pancreatic tumors.
Specific exposure of ICU staff to SARS-CoV-2 seropositivity: a wide seroprevalence study in a French city-center hospital
Authors: Vivier Emmanuel , Pariset Caroline , Rio Stephane , Armand Sophie , Doroszewski Fanny , Richard Delphine , Chardon Marc , Romero Georges , Metral Pierre , Pecquet Matthieu , Didelot Adrien
Published: May 2021

Background

Most hospital organizations have had to face the burden of managing the ongoing COVID-19 outbreak. One of the challenges in overcoming the influx of COVID-19 patients is controlling patient-to-staff transmission. Measuring the specific extent of ICU caregiver exposure to the virus and identifying the associated risk factors are, therefore, critical issues. We prospectively studied SARS-CoV-2 seroprevalence in the staff of a hospital in Lyon, France, several weeks after a first epidemic wave. Risk factors for the presence of SARS-CoV-2 antibodies were identified using a questionnaire survey.

Results

The overall seroprevalence was 9% (87/971 subjects). Greater exposure was associated with higher seroprevalence, with a rate of 3.2% [95% CI 1.1–5.2%] among non-healthcare staff, 11.3% [8.9–13.7%] among all healthcare staff, and 16.3% [12.3–20.2%] among healthcare staff in COVID-19 units. The seroprevalence was dramatically lower (3.7% [1.0–6.7%]) in the COVID-19 ICU. Risk factors for seropositivity were contact with a COVID-19-confirmed household (odds ratio (OR), 3.7 [1.8–7.4]), working in a COVID-19 unit (OR, 3.5 [2.2–5.7], and contact with a confirmed COVID-19 coworker (OR, 1.9 [1.2–3.1]). Conversely, working in the COVID-19-ICU was negatively associated with seropositivity (OR, 0.33 [0.15–0.73]).

Conclusions

In this hospital, SARS-CoV-2 seroprevalence was higher among staff than in the general population. Seropositivity rates were particularly high for staff in contact with COVID-19 patients, especially those in the emergency department and in the COVID-19 unit, but were much lower in ICU staff.

Clinical trial registration NCT04422977