bluuebunny/crossref_metadata_2025 huggingface dataset:
The unequal effects of austerity measures between income-groups on the access to healthcare: a quasi-experimental approach
Authors: Torfs Lore , Adriaenssens Stef , Lagaert Susan , Willems Sara
Published: March 2021

Background

The Great Recession, starting in 2008, was characterized by an overall reduction in living standards. This pushed several governments across Europe to restrict expenditures, also in the area of healthcare. These austerity measures are known to have affected access to healthcare, probably unevenly among social groups. This study examines the unequal effects of retrenchment in healthcare expenditures on access to medical care for different income groups across European countries.

Method

Using data of two waves (2008 and 2014) of the European Union Statistics of Income and Living Conditions survey (EU-SILC), a difference-in-differences (DD) approach was used to analyse the overall change in unmet medical needs over time within and between countries. By adding another interaction, the differences in the effects between income quintiles (difference-in-difference-in-differences: DDD) were estimated. To do so, comparisons between two pairs of a treatment and a control case were made: Iceland versus Sweden, and Ireland versus the United Kingdom. These comparisons are made between countries with recessions equal in magnitude, but with different levels of healthcare cuts. This strategy allows isolating the effect of cuts, net of the severity of the recession.

Results

The DD-estimates show a higher increase of unmet medical needs during the Great Recession in the treatment cases (Iceland vs. Sweden: + 3.24 pp.; Ireland vs. the United Kingdom: + 1.15 pp). The DDD-estimates show different results over the two models. In Iceland, the lowest income groups had a higher increase in unmet medical needs. This was not the case in Ireland, where middle-class groups saw their access to healthcare deteriorate more.

Conclusion

Restrictions on health expenditures during the Great Recession caused an increase in self-reported unmet medical needs. The burden of these effects is not equally distributed; in some cases, the lower-income groups suffer most. The case of Ireland, nevertheless, shows that certain policy measures may relatively spare lower-income groups while affecting middle-class income groups more. These results bring in evidence that policies can reduce and even overshoot the general effect of income inequalities on access to healthcare.
Variation in the use of percutaneous coronary interventions among older patients with acute coronary syndromes: a multilevel study in Fukuoka, Japan
Authors: Li Yunfei , Babazono Akira , Jamal Aziz , Fujita Takako , Yoshida Shinichiro , Kim Sung-A
Published: March 2021

Background

Variation in health care delivery among regions and hospitals has been observed worldwide and reported to have resulted in health inequalities. Regional variation of percutaneous coronary intervention (PCI) was previously reported in Japan. This study aimed to assess the small-area and hospital-level variations and to examine the influence of patient and hospital characteristics on the use of PCI.

Methods

Data provided by the Fukuoka Prefecture Latter-stage Elderly Insurance Association was used. There were 11,821 patients aged ≥65 years with acute coronary syndromes who were identified from 2015 to 2017. Three-level multilevel logistic regression analyses were performed to quantify the small-area and hospital variations, as well as, to identify the determinants of PCI use.

Results

The results showed significant variation (δ2 = 0.744) and increased PCI use (MOR = 2.425) at the hospital level. After controlling patient- and hospital-level characteristics, a large proportional change in cluster variance was found at the hospital level (PCV 14.7%). Fixed-effect estimation results showed that females, patients aged ≥80 years old, hypertension and dyslipidemia had significant association with the use of PCI. Hospitals with high physician density had a significantly positive relationship with PCI use.

Conclusions

Patients receiving care in hospitals located in small areas have equitable access to PCI. Hospital-level variation might be originated from the oversupply of physicians. A balanced number of physicians and beds should be taken into consideration during healthcare allocation. A treatment process guideline on PCI targeting older patients is also needed to ensure a more equitable access for healthcare resources.
The laboratory findings and different COVID-19 severities: a systematic review and meta-analysis
Authors: Kazemi Erfan , Soldoozi Nejat Reihane , Ashkan Fatemeh , Sheibani Hossein
Published: March 2021

Background

Abnormal laboratory findings are common in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this systematic review was to investigate the effect of the level of some laboratory factors (C-reactive protein (CRP), creatinine, leukocyte count, hemoglobin, and platelet count) on the severity and outcome of coronavirus disease 2019 (COVID-19).

Methods

We searched PubMed, Web of Science, Scopus, and Google Scholar. We collected the articles published before May 26, 2020. We gathered the laboratory factors in groups of patients with COVID-19, and studied the relation between level of these factors with severity and outcome of the disease.

Results

Mean CRP level, creatinine, hemoglobin, and the leukocytes count in the critically ill patients were significantly higher than those of the other groups (non-critical patients); mean CRP = 54.81 mg/l, mean creatinine = 86.82 μmol/l, mean hemoglobin = 144.05 g/l, and mean leukocyte count = 7.41 × 109. The lymphocyte count was higher in patients with mild/moderate disease (mean: 1.32 × 109) and in the invasive ventilation group (mean value of 0.72 × 109), but it was considerably lower than those of the other two groups. The results showed that the platelet count was higher in critically ill patients (mean value of 205.96 × 109). However, the amount was lower in the invasive ventilation group compared with the other groups (mean level = 185.67 × 109).

Conclusion

With increasing disease severity, the leukocyte count and the level of CRP increase significantly and the lymphocyte count decreases. There seems to be a significant relation between platelet level, hemoglobin, and creatinine level with severity of the disease. However, more studies are required to confirm this.
The clinical significance of CTC enrichment by GPC3-IML and its genetic analysis in hepatocellular carcinoma
Authors: Yi Bin , Wu Tian , Zhu Nan , Huang Yao , Yang Xiaoyu , Yuan Lei , Wu Yingjun , Liang Xiaofei , Jiang Xiaoqing
Published: March 2021

Background

This research was to develop a special method for enriching Circulating tumor cells (CTCs) of Hepatocellular carcinoma (HCC) by Glypican-3 immunoliposomes (GPC3-IML), and to analyze the correlation between the CTCs count and tumor malignancy, as well as to investigate the mutation characteristics of CTC-derived NGS.

Results

In this study characterization of physical parameters was performed with the preparation of GPC3-IML. CTCs in peripheral blood of HCC patients were further separated and identified. Immunofluorescence was used to identify CTCs for further counting. By this means, the correlation between CTCs count and clinicopathological features was analyzed, and the genetic mutation characteristics of NGS derived from CTCs were investigated and compared with that of tissue NGS. Results showed that compared with EpCAM and vimentin, GPC-3 had a stronger CTCs separation ability. There was a correlation between "positive" count of CTCs (≥ 5 PV-CTC per 7.5 ml blood) and BCLC stage (P = 0.055). The result of CTC-NGS was consistent with that of tissue-NGS in 60% cases, revealing thatKMT2Cwas a common highly-frequent mutated gene.

Conclusion

The combination of immunomagnetic separation of CTCs and anti-tumor marker identification technology can be regarded as a new technology of CTCs detection in peripheral blood of patients with HCC.

Trial registrationEHBHKY2020-k-024. Registered 17 August 2020—Retrospectively registered
Cross-cultural adaptation, validity and reliability of the Chinese Version of Miller Behavioral Style Scale
Authors: Zhuo Qiqi , Cui Changsheng , Liang Hongmin , Bai Yangjuan , Hu Qiulan , Hanum Ardani Latifah , Yang Mingfang , Wang Yanjiao , Wei Wei , Ding Lan , Ma Fang
Published: March 2021

Background

Health education basing on patients’ information-seeking styles can improve the effectiveness of health education and patients’ health outcomes. The Miller Behavioral Style Scale (MBSS) is widely used to identify individual’s information-seeking styles, but the Chinese version is lacking. The study aim was to translate and culturally adapt the MBSS into Chinese version and test the content validity, construct validity and internal consistency reliability of the Chinese version of MBSS (C-MBSS).

Methods

The forward-back-translation procedure was adopted in the translation of the MBSS. Content validity was assessed in a panel of experts. In a sample of 1343 individuals including patients, patients’ caregivers, university students, and medical staff, reliability and construct validity were assessed using Cronbach’s alpha coefficient and factor analysis. The measurement invariance across samples was tested using multigroup confirmatory factor analysis (MGCFA). Floor and ceiling effects were checked.

Results

The C-MBSS achieved conceptual and semantic equivalence with the original scale. The item-level content validity index (I-CVI) of each item ranged from 0.78 to 1, and the averaging scale-level content validity index (S-CVI/ Ave) was 0.95. The exploratory factor analysis resulted in 2-factor assumption for each hypothetical threat-evoking scenario. Confirmatory factor analysis demonstrated a good fit between theoretical model and data, which provided confirmatory evidence for the second-order factor structure of 2-factor solution (Monitoring and Blunting). The Cronbach's alpha coefficients for the Monitoring and Blunting sub-scales of the C-MBSS were 0.75 and 0.62 respectively. MGCFA results supported the measurement invariance for the Monitoring sub-scale of the C-MBSS across samples. No floor or ceiling effects occurred.

Conclusions

This study indicates that the C-MBSS has good content and construct validity. The Monitoring sub-scale of the C-MBSS had acceptable internal consistency reliability while the Blunting sub-scale had unsatisfactory one, which suggest that the Monitoring sub-scale of the C-MBSS can be used to identify individuals’ information-seeking styles in Chinese contexts across different populations.
Identification of the Urogenital Distress Inventory-6 and the Incontinence Impact Questionnaire-7 cutoff scores in urinary incontinent women
Authors: Skorupska Katarzyna , Grzybowska Magdalena Emilia , Kubik-Komar Agnieszka , Rechberger Tomasz , Miotla Pawel
Published: March 2021

Purpose

Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire-7 (IIQ-7) and The International Consultation on Incontinence (ICIQ-SF) Short Form are used to diagnose individuals with urinary incontinence (UI) and to assess the impact of the dysfunction on patient quality of life. While ICIQ-SF has fixed cutoff values—UDI-6 and IIQ-7 do not. We aimed to find the cutoff scores for UDI-6 and IIQ-7 in women with UI.

Methods

The study involved 205 women aged between 31 and 83 years—155 with, and 50 without UI symptoms. All participants completed all three questionnaires: ICIQ-SF, UDI-6 and IIQ-7. Patients were categorized according to their ICIQ-SF scores, as symptomatic ICIQ-SF ≥ 6 (n = 134) and asymptomatic ICIQ < 6 (n = 60). The Receiver Operating Characteristics (ROC) curve was used to test how well UDI-6 allowed a discrimination between patients suffering from UI and those who do not. Area under Curve (AUC) statistic was calculated to measure the UDI-6 and IIQ-7 Total Score efficiency.

Results

The cutoff values were selected. On the basis of the ROC curve analysis, the UDI-6 Total Score of 33.33 and IIQ-7 Total Score of 9.52 were determined to be the optimal cutoff for distinguishing between symptomatic and asymptomatic women (AUC = 0.94-UDI-6 and 0.91-IIQ-7).

Conclusions

For UDI-6 scores more than 33.33 indicate higher distress caused by UI symptoms. Moreover, the higher impact of UI on health- related quality of life is seen in women who scored 9 or more in the IIQ-7 questionnaire, and such women felt impaired quality of life.

Trial registration number NCT04433715, 11.06.2020 “retrospectively registered”.
Impacts of Cyclosporin A on clinical pregnancy outcomes of patients with a history of unexplained transfer failure: a retrospective cohort study
Authors: Qu Danni , Tian Xiangming , Ding Ling , Li Yuan , Zhou Wenhui
Published: March 2021

Background

A rapid development in assisted reproductive technology (ART) has led to a surge in its popularity among target couples. However, elucidation on the molecular mechanism and effective solutions for a common problem posed by ART, namely transfer failure, is still lacking. The new therapeutic potential of cyclosporin A (CsA), a typical immunosuppressant widely used in the treatment of rejection after organ transplantation, in recurrent pregnancy loss (RPL) patients may inspire some novel transfer failure therapies in the future. To further explore the clinical effects of CsA, this study investigated whether its application can improve clinical pregnancy outcomes in patients with a history of unexplained transfer failure in frozen-thawed embryo transfer (FET) cycles.

Methods

Data from a retrospective cohort investigation (178 frozen-thawed embryo transfer cycles in 178 patients) were analysed using binary logistic regression to explore the relationship between CsA treatment and clinical pregnancy outcomes; the odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated as a measure of relevancy. Implantation rate was the main outcome measure.

Results

There was no difference in the fine adjusted OR (95 % CI) of the implantation rate [1.251 (0.739–2.120)], clinical pregnancy rate [1.634 (0.772–3.458)], chemical pregnancy rate [1.402 (0.285–6.909)], take-home baby rate [0.872 (0.423–1.798)], multiple births rate [0.840 (0.197–3.590)], preterm birth [1.668 (0.377–7.373)], abnormal birth weight [1.834 (0.533–6.307)] or sex ratio [0.956 (0.339–2.698)] between the CsA-treated group and control group. No birth defects were observed in the present study.

Conclusions

Although CsA does not affect infant characteristics, it has no beneficial effects on the clinical pregnancy outcomes in patients with a history of unexplained transfer failure in FET cycles.
Creating a measure to operationalize engaged well-being at work
Authors: Bosle Catherin , Fischer Joachim E. , Herr Raphael M.
Published: March 2021

Background

Mental well-being and work engagement are both desirable, positive states of mind that help employees to better function in the workplace. While occupational researchers have argued in favor of considering both states concurrently, it is less clear how this might be translated to provide an instrument characterizing the workforce accordingly. The present study describes empirical efforts to operationalize a construct called engaged well-being.

Methods

We used employee-level data (n = 13,538) from three waves of the German linked personnel panel (LPP; 2012–2017). Exploratory factor analysis and a combination of hierarchical and non-hierarchical cluster analyses linked with within-sum-of-squares statistics were used to identify distinct profiles describing mental well-being and work engagement concurrently. These profiles were then used as the basis to identify cut-offs to create replicable categories of engaged well-being. Using the longitudinal data from a subgroup providing data across more than one wave, we observed whether the newly constructed indicator changed over time.

Results

The exploratory factor analysis suggested that both states were two distinct factors. Cluster analysis linked with within-sum-of-squares statistics suggested a four-cluster solution: engaged well-being (46.9%), disengaged well-being (27.5%), engaged strain (8.8%), and disengaged strain (16.8%). One cut-off for each state was identified to replicate the cluster solution. Across observation periods, we could observe changes in engaged well-being.

Conclusions

Our measure of engaged well-being can be used to simultaneously characterize a workforce’s mental well-being and work engagement. Changes in this measure over time suggest its potential utility in organizational interventions. Future studies are needed to further explore both the antecedents, correlates, and potential effects of engaged well-being.
The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex
Authors: Wang Xin , Jiang Wei , Luo Shuo , Yang Xiaoyu , Wang Changnan , Wang Bingying , Dang Yongjun , Shen Yin , Ma Dengke K.
Published: March 2021

TMEM132Dis a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Defining a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the soleTMEM132ortholog inC. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations inC. elegans tmem-132that disrupt interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects intmem-132mutants, whereas gain-of-function ofTMEM132Din mammalian cells inhibits WRC, leading to decreased abundance of select WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.
Long non‐coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer
Authors: Hu Chuan-yi , Chen Juan , Qin Xin-hua , You Pan , Ma Jie , Zhang Jing , Zhang He , Xu Ji-dong
Published: March 2021

Background

Bone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa.

Methods

NORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD.

Results

PCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells.

Conclusions

NORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.
YAP promotes autophagy and progression of gliomas via upregulating HMGB1
Authors: Zhao Min , Zhang Yu , Jiang Yang , Wang Kai , Wang Xiang , Zhou Ding , Wang Yan , Yu Rutong , Zhou Xiuping
Published: March 2021

Background

Due to the hypoxia and nutrient deficiency microenvironment, glioblastoma (GBM) exhibits high autophagy activity and autophagy plays an important role in the progression of GBM. However, the molecular mechanism of autophagy in GBM progression remains unclear. The aim of this study is to delve out the role and mechanism of yes-associated protein (YAP) in GBM autophagy and progression.

Methods

The level of autophagy or autophagy flux were assessed by using western blotting, GFP-LC3 puncta (Live) imaging, transmission electron microscopy and GFP-RFP-LC3 assay. The GBM progression was detected by using CCK8, EdU, nude mouse xenograft and Ki67 staining. Isobaric tags for relative and absolute quantification (iTraq) quantitative proteomics was used to find out the mediator of YAP in autophagy. Expression levels of YAP and HMGB1 in tissue samples from GBM patients were examined by Western blotting, tissue microarray and immunohistochemistry.

Results

YAP over-expression enhanced glioma cell autophagy under basal and induced conditions. In addition, blocking autophagy by chloroquine abolished the promoting effect of YAP on glioma growth. Mechanistically, YAP over-expression promoted the transcription and translocation of high mobility group box 1(HMGB1), a well-known regulator of autophagy, from nucleus to cytoplasm. Down-regulation of HMGB1 abolished the promoting effect of YAP on autophagy and glioma growth. Furthermore, the expression of YAP and HMGB1 were positively associated with each other and suggested poor prognosis for clinical GBM.

Conclusion

YAP promoted glioma progression by enhancing HMGB1-mediated autophagy, indicating that YAP-HMGB1 axis was a feasible therapeutic target for GBM. Our study revealed a clinical opportunity involving the combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression.
Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression
Authors: Gao Pan , Lyu Qing , Ghanam Amr R. , Lazzarotto Cicera R. , Newby Gregory A. , Zhang Wei , Choi Mihyun , Slivano Orazio J. , Holden Kevin , Walker John A. , Kadina Anastasia P. , Munroe Rob J. , Abratte Christian M. , Schimenti John C. , Liu David R. , Tsai Shengdar Q. , Long Xiaochun , Miano Joseph M.
Published: March 2021

Background

Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (HDR) versus the recently reported prime editing 2 (PE2) system was carried out in mice over a TFBS called a CArG box in the Tspan2 promoter.

Results

Quantitative RT-PCR showed loss of Tspan2 mRNA in aorta and bladder, but not heart or brain, of mice homozygous for an HDR-mediated three base pair substitution in the Tspan2 CArG box. Using the same protospacer, mice homozygous for a PE2-mediated single-base substitution in the Tspan2 CArG box displayed similar cell-specific loss of Tspan2 mRNA; expression of an overlapping long noncoding RNA was also nearly abolished in aorta and bladder. Immuno-RNA fluorescence in situ hybridization validated loss of Tspan2 in vascular smooth muscle cells of HDR and PE2 CArG box mutant mice. Targeted sequencing demonstrated variable frequencies of on-target editing in all PE2 and HDR founders. However, whereas no on-target indels were detected in any of the PE2 founders, all HDR founders showed varying levels of on-target indels. Off-target analysis by targeted sequencing revealed mutations in many HDR founders, but none in PE2 founders.

Conclusions

PE2 directs high-fidelity editing of a single base in a TFBS leading to cell-specific loss in expression of an mRNA/long noncoding RNA gene pair. The PE2 platform expands the genome editing toolbox for modeling and correcting relevant noncoding SNVs in the mouse.
Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma
Authors: Yu Jie , Chai Peiwei , Xie Minyue , Ge Shengfang , Ruan Jing , Fan Xianqun , Jia Renbing
Published: March 2021

Background

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.

Results

Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.

Conclusion

We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.
Patient experiences of receiving arthroscopic surgery or personalised hip therapy for femoroacetabular impingement in the context of the UK fashion study: a qualitative study
Authors:   on behalf of the UK FASHIoN study group, Realpe A. X. , Foster N. E. , Dickenson E. J. , Jepson M. , Griffin D. R. , Donovan J. L.
Published: March 2021

Background

UK FASHIoN was a multicentre randomised controlled trial comparing hip arthroscopic surgery (HA) with personalised hip therapy (PHT, physiotherapist-led conservative care), for patients with hip pain attributed to femoroacetabular impingement (FAI) syndrome. Our aim was to describe the treatment and trial participation experiences of patients, to contextualise the trial results and offer further information to assist treatment decision-making in FAI.

Methods

We conducted in-depth semi-structured telephone interviews with a purposive sample of trial participants from each of the trial arms. They were interviewed after they received treatment and completed their first year of trial participation. Thematic analysis and constant comparison analytical approaches were used to identify themes of patient treatment experiences during the trial.

Results

Forty trial participants were interviewed in this qualitative study. Their baseline characteristics were similar to those in the main trial sample. On average, their hip-related quality of life (iHOT-33 scores) at 12 months follow-up were lower than average for all trial participants, indicating poorer hip-related quality of life as a consequence of theoretical sampling. Patient experiences occurred in five patient groups: those who felt their symptoms improved with hip arthroscopy, or with personal hip therapy, patients who felt their hip symptoms did not change with PHT but did not want HA, patients who decided to change from PHT to HA and a group who experienced serious complications after HA. Interviewees mostly described a trouble-free, enriching and altruistic trial participation experience, although most participants expected more clinical follow-up at the end of the trial.

Conclusion

Both HA and PHT were experienced as beneficial by participants in the trial. Treatment success appeared to depend partly on patients’ prior own expectations as well as their outcomes, and future research is needed to explore this further. Findings from this study can be combined with the primary results to inform future FAI patients.

Trial registration

Arthroscopic surgery for hip impingement versus best conventional care (ISRCTN64081839). 28/02/2014.
Napping on the night shift and its impact on blood pressure and heart rate variability among emergency medical services workers: study protocol for a randomized crossover trial
Authors: Patterson P. Daniel , Weiss Leonard S. , Weaver Matthew D. , Salcido David D. , Opitz Samantha E. , Okerman Tiffany S. , Smida Tanner T. , Martin Sarah E. , Guyette Francis X. , Martin-Gill Christian , Callaway Clifton W.
Published: March 2021

Background

There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs.

Methods

We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%.

Discussion

Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact.

Trial registration

ClinicalTrials.govNCT04469803. Registered on 9 July 2020
Single-step ethanol production from raw cassava starch using a combination of raw starch hydrolysis and fermentation, scale-up from 5-L laboratory and 200-L pilot plant to 3000-L industrial fermenters
Authors: Krajang Morakot , Malairuang Kwanruthai , Sukna Jatuporn , Rattanapradit Krongchan , Chamsart Saethawat
Published: March 2021

Background

A single-step ethanol production is the combination of raw cassava starch hydrolysis and fermentation. For the development of raw starch consolidated bioprocessing technologies, this research was to investigate the optimum conditions and technical procedures for the production of ethanol from raw cassava starch in a single step. It successfully resulted in high yields and productivities of all the experiments from the laboratory, the pilot, through the industrial scales. Yields of ethanol concentration are comparable with those in the commercial industries that use molasses and hydrolyzed starch as the raw materials.

Results

Before single-step ethanol production, studies of raw cassava starch hydrolysis by a granular starch hydrolyzing enzyme, StargenTM002, were carefully conducted. It successfully converted 80.19% (w/v) of raw cassava starch to glucose at a concentration of 176.41 g/L with a productivity at 2.45 g/L/h when it was pretreated at 60 °C for 1 h with 0.10% (v/w dry starch basis) of Distillase ASP before hydrolysis. The single-step ethanol production at 34 °C in a 5-L fermenter showed that Saccharomyces cerevisiae (Fali, active dry yeast) produced the maximum ethanol concentration, pmax at 81.86 g/L (10.37% v/v) with a yield coefficient, Yp/s of 0.43 g/g, a productivity or production rate, rp at 1.14 g/L/h and an efficiency, Ef of 75.29%. Scale-up experiments of the single-step ethanol production using this method, from the 5-L fermenter to the 200-L fermenter and further to the 3000-L industrial fermenter were successfully achieved with essentially good results. The values of pmax,Yp/s, rp, and Ef of the 200-L scale were at 80.85 g/L (10.25% v/v), 0.42 g/g, 1.12 g/L/h and 74.40%, respectively, and those of the 3000-L scale were at 70.74 g/L (8.97% v/v), 0.38 g/g, 0.98 g/L/h and 67.56%, respectively. Because of using raw starch, major by-products, i.e., glycerol, lactic acid, and acetic acid of all three scales were very low, in ranges of 0.940–1.140, 0.046–0.052, 0.000–0.059 (% w/v), respectively, where are less than those values in the industries.

Conclusion

The single-step ethanol production using the combination of raw cassava starch hydrolysis and fermentation of three fermentation scales in this study is practicable and feasible for the scale-up of industrial production of ethanol from raw starch.
Overproduction of docosahexaenoic acid in Schizochytrium sp. through genetic engineering of oxidative stress defense pathways
Authors: Han Xiao , Li Zhaohui , Wen Ying , Chen Zhi
Published: March 2021

Background

Oxidation and peroxidation of lipids in microorganisms result in increased levels of intracellular reactive oxygen species (ROS) and reactive aldehydes, and consequent reduction of cell growth and lipid accumulation.

Results

To reduce oxygen-mediated cell damage and increase lipid and docosahexaenoic acid (DHA) production in Schizochytrium sp., we strengthened the oxidative stress defense pathways. Overexpression of the enzymes thioredoxin reductase (TRXR), aldehyde dehydrogenase (ALDH), glutathione peroxidase (GPO), and glucose-6-phosphate dehydrogenase (ZWF) strongly promoted cell growth, lipid yield, and DHA production. Coexpression of ZWF, ALDH, GPO, and TRXR enhanced ROS-scavenging ability. Highest values of dry cell weight, lipid yield, and DHA production (50.5 g/L, 33.1 g/L, and 13.3 g/L, respectively) were attained in engineered strain OaldH-gpo-trxR by shake flask fed-batch culture; these were increases of 18.5%, 80.9%, and 114.5% relative to WT values.

Conclusions

Our findings demonstrate that engineering of oxidative stress defense pathways is an effective strategy for promoting cell robustness, lipid yield, and DHA production in Schizochytrium.
Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis
Authors: Ueno Masanobu , Miyagawa Ippei , Nakano Kazuhisa , Iwata Shigeru , Hanami Kentaro , Fukuyo Shunsuke , Kubo Satoshi , Miyazaki Yusuke , Kawabe Akio , Yoshinari Hiroko , Nakayamada Shingo , Tanaka Yoshiya
Published: March 2021

Background

Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of MPZ (300 mg) for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings.

Methods

We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (Post-MPZ). We also retrospectively collected data from the same patients for the 12 months before the administration of MPZ (Pre-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil counts, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Pre-MPZ and Post-MPZ.

Results

The 12-month remission rate after the initiation of MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose over time in the Pre-MPZ group, whereas all these parameters were significantly decreased over time in the Post-MPZ group. The number of patients using concomitant immunosuppressant also decreased over time in the Post-MPZ group. VDI did not increase in either group. The MPZ retention rate was 100% and only three patients (18.8%) had infections. Changes in BVAS, eosinophil count, and cumulative concomitant CS dose were significantly lower in the Post-MPZ group than in the Pre-MPZ group. There was no significant difference in the changes in VDI between the groups.

Conclusion

This study demonstrated that MPZ is effective and safe for EGPA. Furthermore, MPZ decreases disease activity, increases remission rate, and has a CS-sparing effect.
Does kinesiotaping can improve static stability of the knee after anterior cruciate ligament rupture? A randomized single-blind, placebo‐controlled trial
Authors: Ogrodzka-Ciechanowicz Katarzyna , Głąb Grzegorz , Ślusarski Jakub , Gądek Artur , Nawara Jolanta
Published: March 2021

Background

The aim of the study was the assessment of the early impact of the selected kinesiotaping technique on the static stability of the knee joint in patients with ACL rupture on the basis of stabilographic parameters.

Methods

Sixty-two patients with a complete ACL rupture (32 patients in experimental group and 30 patients in placebo group) took part in the randomized single-blind, placebo-controlled trial. The ligament technique of KT was taken into consideration. Application of a KT tape only on the injured knee was to stabilize the knee joint. Experimental group had application of KT on the injured knee and the placebo group had a KT placebo application (with no tension on KT). Intervention and stabilographic test in both groups was the same.

Research tools included measurements of static stabilographic parameters on stabilometric platform CQStab2P®. Outcome measures were assessed before intervention and after KT application. The analysis included evaluation of outcome variables – total path length, (SP), statokinesiogram path length in the XY axes (SPML, SPAP), and mean velocities in the XY axes (MV, MVML, MVAP).

Results

The results show a statistically significant shortening of the SP, SPAP and SPML variables only in experimental group. In the placebo group the results were not significant. The analysis also showed a significant improvement in all analyzed variables in the experimental group compared to the healthy side. In the placebo group, the results did not improve significantly after KT application compared to the healthy side.

Conclusions

Application o

f KT in patients after ACL rupture shortened the total path length and improved the value of parameters in the frontal and sagittal planes in experimental group, which may suggest the potentially greater improvement in these parameters. By improving the values of the analyzed variables, the KT application is able to compensate for the loss of static stability of the knee.

Trial Registration

This study was registered retrospectively in the Australian New Zealand Clinical Trials Registry (ANZCTR). Registration number: ACTRN12616001407482.
Benefits of autologous platelet tissue graft in wound healing after corneal refractive surgery: a case report
Authors: Takayanagi Yoshinori , Kato Shigeaki , Okada Masaru
Published: March 2021

Background

Corneal refractive surgeries cause epithelial damage and induce wound healing processes. To promote wound healing after photorefractive keratectomy, the effectiveness of an autologous platelet tissue graft was assessed.

Case presentation

A 45-year-old Asian male with low myopia and/or myopic astigmatism received photorefractive keratectomy in both eyes. The right eye was postoperatively treated with an autologous platelet tissue graft using the GPS III Platelet Concentration System to prepare platelet-rich plasma, while the left eye was not treated. Both eyes achieved the expected uncorrected distance visual acuity, but the platelet-rich-plasma-treated right eye obtained improved visual acuity more than 1 week before the untreated left eye. Perceived pain after photorefractive keratectomy was much lower and of shorter duration in the treated right eye than it was for the left eye. Pericorneal injection on the bulbar conjunctiva with superficial keratitis resolved earlier in the right eye than the left eye.

Conclusions

Autologous platelet tissue grafting using a GPS III to obtain platelet-rich plasma was effective in promoting corneal wound healing after photorefractive keratectomy. Thus, platelet-rich plasma may be beneficial for patients undergoing corneal refractive surgeries.
Negative-pressure-related diffuse alveolar hemorrhage after monitored anesthesia care for vertebroplasty: a case report
Authors: Jo Yumin , Hwang Jagyung , Lee Jieun , Kang Hansol , Hong Boohwi
Published: March 2021

Background

Diffuse alveolar hemorrhage (DAH) is a rare, life-threatening condition that can present as a spectrum of nonspecific symptoms, ranging from cough, dyspnea, and hemoptysis to severe hypoxemic respiratory failure. Perioperative DAH is frequently caused by negative pressure pulmonary edema resulting from acute airway obstruction, such as laryngospasm, although hemorrhage itself is rare.

Case presentation

This case report describes an unexpected hemoptysis following monitored anesthesia care for vertebroplasty. A 68-year-old Asian woman, with a compression fracture of the third lumbar vertebra was admitted for vertebroplasty. There were no noticeable events during the procedure. After the procedure, the patient was transferred to the postanesthesia care unit (PACU), at which sudden hemoptysis occurred. The suspected airway obstruction may have developed during transfer or immediate arrive in PACU. In postoperative chest x-ray, newly formed perihilar consolidation observed in both lung fields. The patients was transferred to a tertiary medical institution for further evaluation. She diagnosed with DAH for hemoptysis, new pulmonary infiltrates on chest x-ray and anemia. The patient received supportive care and discharged without further events.

Conclusions

Short duration of airway obstruction may cause DAH, it should be considered in the differential diagnosis of postoperative hemoptysis of unknown etiology.
Analyses of the pericyte transcriptome in ischemic skeletal muscles
Authors: Teng Yuan-chi , Porfírio-Sousa Alfredo Leonardo , Ribeiro Giulia Magri , Arend Marcela Corso , da Silva Meirelles Lindolfo , Chen Elizabeth Suchi , Rosa Daniela Santoro , Han Sang Won
Published: March 2021

Background

Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions.

Methods

In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing.

Results

Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells.

Conclusions

Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.
Apoptosis repressor with caspase recruitment domain (ARC) promotes bone regeneration of bone marrow-derived mesenchymal stem cells by activating Fgf-2/PI3K/Akt signaling
Authors: Hu Longwei , Wang Yang , Pan Hongya , Kadir Kathreena , Wen Jin , Li Siyi , Zhang Chenping
Published: March 2021

Objectives

This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).

Materials and methods

The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs.

Results

ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway.

Conclusions

The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.
Distraction sinking and fossilized coleoid predatory behaviour from the German Early Jurassic
Authors: Klug Christian , Schweigert Günter , Fuchs Dirk , De Baets Kenneth
Published: March 2021

Exceptional fossil preservation is required to conserve soft-bodied fossils and even more so to conserve their behaviour. Here, we describe a fossil of a co-occurrence of representatives of two different octobrachian coleoid species. The fossils are from the Toarcian Posidonienschiefer of Ohmden near Holzmaden, Germany. The two animals died in the act of predation, i.e. one had caught the other and had begun to nibble on it, when they possibly sank into hypoxic waters and suffocated (distraction sinking). This supports the idea that primitive vampyromorphs pursued diverse feeding strategies and were not yet adapted to being opportunistic feeders in oxygen minimum zones like their modern relative Vampyroteuthis.