bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with perceived barriers of health care access among reproductive-age women in Ethiopia: a Secondary data analysis of 2016 Ethiopian Demographic and Health Survey
Authors: Tamirat koku , Tessema Zemenu Tadesse , Kebede Fentahun Bikale
Published: April 2020

Background: Health care access is the timely use of personal health services to achieve the best health outcomes. Difficulties to access health care among reproductive-age women may lead to different negative health outcomes like death and disability. Therefore, this study aimed to assess factors associated with perceived barriers of health care access among reproductive-age women in Ethiopia.
Method: This study was based on the 2016 Ethiopia Demography and Health Survey. Individual women record (IR) file was used to extract the dataset and 15, 683 women were included in the final analysis. A composite variable of health care perceived barriers were created from four questions used to rate health care access perceived barriers among reproductive-age women. The Generalized Estimating Equation (GEE) model was fitted to identify factors associated with health care perceived barriers. Crude and Adjusted odds ratio with a 95% CI computed to assess the strength of association between independent and outcome variables.
Result: This study revealed that the perceived barrier of health care access among reproductive age women found to be 69.9% with 95%CI (69.3 to 70.7) to at least one or more of the four reasons. Rural residence (AOR= 2.13, 95%CI: 1.79 to 2.53), age 35-49 years (AOR= 1.24, 95%CI: 1.09 to 1.40), divorced/separated (AOR= 1.34, 95%CI: 1.17 to 1.54), had no health insurance coverage (AOR=1.19, 95%CI: 1.01 to 1.45), poor (AOR=2.09,95%CI: 1.86 to 2.35) and middle wealth (AOR=1.57,95%CI:1.38 to 1.79), no education (AOR=2.30, 95%CI:1.95 to 2.72), primary education (AOR= 1.84, 95%CI :1.58 to 2.15) and secondary education (AOR= 1.31, 95%CI: 1.13 to 1.51) were factors associated with perceived barriers of health care access.
Conclusion: Significant proportion of reproductive-age women faced barriers of health care access, of which, money and distance were the common perceived barriers. Divorced/separated marital status, old age, rural dwelling, no health insurance coverage, low economic status and level of education were factors associated with perceived barriers of health care access. This findings suggests that further strengthening and improvement of health care access to those with low socio-economic status for the realization of universal health coverage and equity of service provision.
The effect of written information and counselling by an advanced practice nurse on resilience in women with vulvar neoplasia during six months after surgical treatment and the influence of social support, recurrence, and age: A secondary analysis of a multicenter randomized controlled trial, WOMAN-PRO-II
Authors: Kofler Sabine , Kobleder Andrea , Ott Stefan , Senn Beate
Published: April 2020

Background: Women with vulvar neoplasia often complain about physical and psychological distress after surgical treatment. Lack of information and support can influence resilience. Whether an information-related intervention through an advanced practice nurse supports resilience and which other factors affect resilience in women with vulvar neoplasia has never been investigated.
Methods: The aims of this study were (a) to analyse whether counselling based on the WOMAN-PRO II program causes a significant improvement in the resilience scores of women with vulvar neoplasia compared to written information and (b) to identify the potential predictors of resilience.
A randomized controlled trial was conducted in women with vulvar neoplasia (n = 49) six months after surgical treatment in four Swiss hospitals and one Austrian hospital. Analyses of resilience and its predictors were performed using a linear mixed model.
Results: Thirty-six women (intervention I, n = 8; intervention II, n = 28) completed the randomized controlled trial. In total, 13 women (26.5%) dropped out of the trial. The resilience score did not differ significantly between the two interventions three and six months after randomisation (p = 0.759). Age (b = .04, p = 0.001), social support (b = .28, p = 0.009), counselling time (b = .03, p = 0.018) and local recurrence (b = −.56, p = 0.009) were identified as significant predictors of resilience in the linear mixed model analyses.
Conclusion: The results indicate that the WOMAN-PRO II program as single intervention does not cause a significant change in the resilience scores of women with vulvar neoplasia six months after surgery. Predictors that promote or minimise resilience have been identified and should be considered when developing resilience programs for women with vulvar neoplasia. A repetition of the study with a larger sample size is recommended.
Predicting factors of adjacent segment degeneration after long-segment spinal fusion: spinopelvic parameters analysis
Authors: Chiu Ping-Yeh , Kao Fu-Cheng , Chen Wen-Jer , Yu Chia-Wei , Niu Chi-Chien , Lai Po-Liang , Tsai Tsung-Ting , Hsieh Ming-Kai
Published: April 2020

Background We investigated whether spinopelvic parameters are important prognostic factors causing adjacent segment degeneration (ASD) after long instrumented spinal fusion for degenerative spinal disease. Methods This uncontrolled, randomized, single arm retrospective study included patients who underwent long instrumented lumbar fusion (fusion levels≥ 4) in the past 5 years with follow-up for at least 2 years. The inclusion criteria included adult patients (≥40 years of age) with a diagnosis of spinal degeneration who underwent instrumented corrective surgery. The exclusion criteria included preexisting adjacent disc degeneration, combined anterior reconstructive surgery, and distal ASD. Clinical and operative characters were evaluated. Angle of lumbar lordosis (LLA), sacral slope (SSA), pelvic tilt (PTA) and pelvic incidence (PIA) were compared preoperatively, postoperatively and at the final follow-up. Results From 2009 to 2014, 60 patients (30 ASD and 30 non-ASD) were enrolled. The average age was 66.82 ± 7.48 years for the study group and 67.97 ± 7.81 years for the control group. There was no statistically significant difference in clinical and operative characteristics. Among all spinopelvic parameters, only pre-, post-operative and final follow-up PIA in ASD group (53.9±10.4ﾟ, 54.6±14.0ﾟ, 54.3±14.1ﾟ) and non-ASD group (60.3±13.0ﾟ, 61.8±11.3ﾟ, 62.5±11.2ﾟ) showed statistically significant differences ( p <0.05). Conclusion This study confirms that preoperative, postoperative and final follow-up PIA is a significant factor contributing to the development of ASD after long instrumented spinal fusion.
Awareness of national malaria management guidelines among house officers in Khartoum state teaching hospitals. Sudan 2018
Authors: Aboshanab Mohammed Altyb Alshykh , New Mohammed Altayeb AbdAlhafeez Mohammed , New Mohamed Elzubair Mohamed Ataelmanan , New Mohammed Alsheekh Alaqbash , New Nagla Abdelrahim Mohamed Ahmed
Published: April 2020

Background

Malaria is a protozoan disease which can lead to serious complications if not treated early and correctly. The aim of this study to assess the knowledge about malaria management guidelines among house officers.

Methods

this is the cross-sectional observational study conducted at 6 of Khartoum teaching hospitals

Results

The study showed that among the 115 participants evaluated there were 70.4% females and 29.6% were males. 94.8% of participants knew there are malaria management guidelines and 5.2% didn't know about the presence of these guidelines, 58.3% have some information and 10.4% just hear about these guidelines. 89.6% knew the management of simple malaria is outpatient management. 65.2% of the participants were aware of where to manage the cases of complicated malaria (inpatient or in ICU). 27.8% of the participants were aware of the management of simple malaria in the second and third trimester.
Improving the diagnosis of common parotid tumors via the combination of CT image biomarkers and clinical parameters
Authors: Zhang Dan , Li Xiaojiao , Lv Liang , Yu Jiayi , Yang Chao , Xiong Hua , Liao Ruikun , Zhou Bi , Huang Xianlong , Liu Xiaoshuang , tang zhuoyue
Published: April 2020

Background : To develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution.
Methods: The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase . Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC).
Results: Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P＜0.05). ROC analysis showed that clinical parameter (age) and quantitative textural IBMs (mean, energy, entropy) were able to categorize the patients into PA group and WT group, with the AUC of 0.784, 0.902, 0.910, 0.805, respectively. When IBMs were added in clinical model, the multivariate models including age-mean and age-energy performed significantly better than the univariate models with the improved AUC of 0.940, 0.944, respectively (P＜0.001).
Conclusion s : Both clinical parameter and CT textural IBMs can be used for the preoperative, noninvasive diagnosis of parotid PA and WT. The diagnostic performance of textural IBM model was obviously better than that of clinical model and conventional image model in this study. While the multivariate model consisted of clinical parameter and textural IBM had the optimal diagnostic performance, which would contribute to the better selection of individualized surgery program.
Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex
Authors: Ju Anes , Fernandez-Arroyo Beatriz , Wu Yifan , Jacky Débora , Beyeler Anna
Published: April 2020

The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.
MtOrt: An empirical mitochondrial amino acid substitution model for evolutionary studies of Orthoptera insects
Authors: Chang Huihui , Nie Yimeng , Zhang Nan , Zhang Xue , Sun Huimin , Mao Ying , Qiu Zhongying , Huang Yuan
Published: April 2020

Background Amino acid substitution models play an important role in inferring phylogenies from mitochondrial proteins. Although different amino acid substitution models have been proposed, only a few were estimated from mitochondrial protein sequences for specific taxa such as the mtArt model for Arthropoda. The increasing of mitochondrial genome data from broad Orthoptera taxa provides an opportunity to estimate the Orthoptera-specific mitochondrial amino acid empirical model. Results We sequenced complete mitochondrial genomes of 54 Orthoptera species, and then estimated an amino acid substitution model (named mtOrt) by maximum likelihood method based on the 283 complete mitochondrial genomes available currently. The results indicated that there are obvious differences between mtOrt and the existing model, and the new model can better fit the Orthoptera mitochondrial protein datasets. Moreover, topologies of trees constructed using mtOrt and existing models are frequently different. MtOrt does indeed have an impact on likelihood improvement as well as tree topologies. The comparisons between the topologies of trees constructed using mtOrt and existing models show that the new model outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein data. Conclusions The new mitochondrial amino acid substitution model of Orthoptera shows obvious differences from the existing models, and outperforms the existing models in inferring phylogenies from Orthoptera mitochondrial protein sequences.
Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells
Authors: Moon Dong Kyu , Kim Bo Gyu , Lee A Ram , Choe Yeong In , New Imran Khan , New Kyoung Mi Moon , Jeon Ryoung-Hoon , Byun June-Ho , Hwang Sun-Chul , Woo Dong Kyun
Published: April 2020

Background: Osteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in up-regulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs.Methods: The optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.Results: Resveratrol treatments above 10 µM seem to have negative effects on cell proliferation and viability of PO-MSCs. Resveratrol treatment (at 5 µM) on PO-MSCs during osteogenic differentiation increased both ALP activities and calcium deposits compared to untreated control groups, demonstrating an enhancing effect of resveratrol on osteogenesis. In addition, resveratrol treatment (at 5 µM) during osteogenic differentiation of PO-MSCs increased both mitochondrial mass and mtDNA copy numbers, indicating that resveratrol can bolster mitochondrial biogenesis in the process of PO-MSC osteogenic differentiation.Conclusion: Taken together, the findings of this study describe roles of resveratrol in promoting osteogenesis and mitochondrial biogenesis of human PO-MSCs suggesting a possible application of resveratrol as a supplement for osteoporosis and/or osteoporotic fractures.
Prognostic value of the miR-200 family in bladder cancer: a systematic review and meta-analysis
Authors: Mei Yanhui , Zheng Jianbo , Xiang Ping , Liu Cheng , Fan Yidong
Published: April 2020

The authors have requested that this preprint be withdrawn due to author disagreement.
Fasciclin-like arabinogalactan gene family in Nicotiana benthamiana: genome-wide identification, classification and expression in response to pathogens
Authors: Wu Xinyang , Lai Yuchao , Lv Lanqing , Ji Mengfei , Han Kelei , Yan Dankan , Lu Yuwen , Peng Jiejun , Rao Shaofei , Yan Fei , Zheng Hongying , Chen Jianping
Published: April 2020

Background: Nicotiana benthamiana is widely used as a model plant to study plant-pathogen interactions. Fasciclin-like arabinogalactan proteins (FLAs), a subclass of arabinogalactan proteins (AGPs), participate in mediating plant growth, development and response to abiotic stress. However, the members of FLAs in N. benthamiana and their response to plant pathogens are unknown.Results: 38 NbFLAs were identified from a genome-wide study. NbFLAs could be divided into four subclasses, and their gene structure and motif composition were conserved in each subclass. NbFLAs may be regulated by cis-acting elements such as STRE and MBS, and could possibly be the targets of transcription factors like C2H2. Quantitative real time polymerase chain reaction (RT-qPCR) results showed that selected NbFLAs were differentially expressed in different tissues. All of the selected NbFLAs were significantly downregulated following infection by turnip mosaic virus (TuMV) and most of them also by Pseudomonas syringae pv tomato (Pst) strain DC3000 (Pst DC3000), suggesting possible roles in response to pathogenic infection.Conclusions: This study systematically identified FLAs in N. benthamiana, and indicates their potential roles in response to biotic stress. The identification of NbFLAs will facilitate further studies of their role in plant immunity in N. benthamiana.
3-Methylxanthine production through biodegradation of theobromine by Aspergillus sydowii
Authors: ZHOU Bin-Xing , Ma Cunqiang , Zheng Chengqin , Xia Tao , Ma Binsong , Liu Xiaohui
Published: April 2020

Background

Methylxanthines including caffeine, theobromine and theophylline are natural and synthetic compounds in tea. Theobromine and other methylxanthine could be metabolized by certain kinds of bacteria and fungi. Previous studies confirmed that several isolates from Pu-erh tea could degrade and convert caffeine and theophylline through N-demethylation and related oxidation, respectively. In this study, seven tea-derived fungi were inoculated into various theobromine agar mediums and liquid mediums to assess their capacity in theobromine utilization. Related metabolites with theobromine degradation were detected by using HPLC in the liquid culture inoculated by candidate isolates to investigate potential application in the production of 3-methylxanthine.

Results

Based on the extent of theobromine utilization, four isolates including Aspergillus niger, Aspergillus sydowii, Aspergillus ustus and Aspergillus tamarii have demonstrated the potential for theobromine biodegradation. Particularly, A. sydowii and A. tamarii could degrade theobromine significantly (p < 0.05) in all given theobromine liquid mediums. 3,7-Dimethyluric acid, 3-methylxanthine, 7-methylxanthine, 3-methyluric acid, xanthine, and uric acid were detected in A. sydowii and A. tamarii culture, respectively, confirming the existence of N-demethylation and oxidation in theobromine catabolism. 3-Methylxanthine was common and main demethylated metabolite of theobromine in A. sydowii and A. tamarii culture. 3-Methylxanthine in A. sydowii culture showed a linear relation with the initial theobromine concentrations that 177.12 ± 14.06 mg/L of 3-methylxanthine was accumulated in TLM-S with 300 mg/L of theobromine. Additionally, pH at 5 and metal ion of Fe 2+ promoted 3-methylxanthine production significantly (p < 0.05).

Conclusions

This study is the first to confirm that A. sydowii and A. tamarii degrade theobromine through N-demethylation and oxidation, respectively. A. sydowii showed the potential application in 3-methylxanthine production with theobromine as feedstock through the N-demethylation at position N-7.
High genetic diversity and strong genetic structure of Strongyllodes variegatus (Coleoptera: Nitidulidae) demonstrate the genetic mechanism of its distribution in oilseed rape production areas in China
Authors: Zhan HaiXia , Hao ZhongPing , Zhou JingJiang , Tang Rui , Zhu LiNi , hou shumin
Published: April 2020

Background : Strongyllodes variegatus (Fairmaire) is a major insect pest of oilseed rape in China. Despite its economic importance, the population genetics of this pest contributing to the development of suitable management and control strategies is poorly known. To understand the population genetics and assess the geographical patterns and genetic structure of S. variegates in China. Using mitochondrial DNA cytochrome c oxidase subunit I and cytochrome b region sequences as genetic markers, we analyzed population genetic diversity and structure from 437 individuals collected in 15 S. variegates populations located in different oilseed rape production areas in China. In addition, we estimated the demographic history using neutrality test and mismatch distribution analysis.
Results : The high level of genetic diversity was detected among the mtDNA region sequences of S. variegates . The population structure analysis strongly suggested that three genetic and geographical regions occur with limited gene flow. The Mantel test showed that the genetic distance was greatly influenced by geographical distance. The demographic analyses showed that S. variegates experienced population fluctuation during the Pleistocene, which was likely to be related to the climatic changes.
Conclusion : Overall, these results demonstrated that the strong population genetic structure of this beetle may attribute to the geographical barriers and subsequently adapt to the regional ecological conditions for the distribution of S. variegates in China.
Keywords : Gene flow, Genetic differentiation, Haplotype, Oilseed rape, Population genetic pattern, Strongyllodes variegates
Everyday work, working culture and patient care. A qualitative study on professionals’ perceptions of the establishment of a specialized brief therapy unit in a district psychiatric center.
Authors: Markussen Hilde Våbenø , Aasdahl Lene , Rise Marit By
Published: April 2020

Background: Increasing mental health problems and a scarcity of treatment resources put pressure on service innovation in mental health services. Innovative efforts include providing brief or short-term treatment to patients who have moderate mental health problems. So far, there is limited knowledge on how implementing brief therapy approaches in mental health organizations influence the professionals and their work. The aim of this study was to explore the professionals’ perceptions on how the establishment of a specialized brief therapy unit in a district psychiatric center had affected the work in the outpatient clinics, specifically the everyday work, working culture and patient care. Methods: Eleven professionals, five men and six women, took part in semi-structured individual interviews. All participants were between 40 and 60 years old and had leading or coordinating positions in the organization. Their professional backgrounds were within psychology, nursing and medicine, most of them specialists in their field. Results: The professionals’ experiences represented four main themes: (1) The brief therapy unit was perceived as successful and celebrated. (2) The general outpatient clinics, on the other hand, were by some, perceived as “forgotten”. (3) The establishment process had elucidated different treatment cultures in the outpatient clinics and had set off (3) a discussion regarding the criteria for prioritizing in mental health services. Conclusion: Implementation of new services calls attention to the distribution of scarce resources and differences in professional cultures. A strong focus on efficiency might challenge professionals’ perceptions of autonomy. Focusing on patients with moderate mental health problems can raise questions concerning resource use and the appropriate level of treatment provision. Before implementing new services, it is important to ensure information and, if possible, understanding for the process in the organization.
Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery
Authors: Lou hanmei , Zhang Xiaojing , Lv Zunfu , Xu Xiaoxian , Yin Zhuomin
Published: April 2020

Objective To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy. Methods We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis. Results Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) >5 ng/ml ( p =0.049 and p =0.013, respectively); moreover, they were much older ( P =0.029) than patients with AC. There were no clinically significant differences in overall survival between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in the three risk groups. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for RFS and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) >5 ng/ml and SCC-Ag >5 ng/ml were independent risk factors for RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had a significantly better RFS and OS ( P =0.036, and P =0.047 for RFS and OS, respectively). Conclusion We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial to survival for intermediate-risk-group patients with ASC, but not those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.
Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant
Authors: Pachetti Maria , Marini Bruna , Benedetti Francesca , Giudici Fabiola , Mauro Elisabetta , Storici Paola , Masciovecchio Claudio , Angeletti Silvia , Ciccozzi Massimo , Gallo Robert Charles , Zella Davide , Ippodrino Rudy
Published: April 2020

Background. SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA Polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. Methods. We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance.Results. We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed that the 14408 mutation, emerged for the first time in Europe in mid-February 2020, is present in the SARS-CoV-2 RdRp gene sequence. Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). Conclusions. These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.
A heuristic model for collaborative practice – Part 1: A meta-synthesis of empirical findings on collaborative strategies in community mental health and substance abuse practice
Authors: Sundet Rolf , Kim Hesook Suzie , Karlsson Bengt , Borg Marit , Sælør Knut Tore , Ness Ottar
Published: April 2020

Background Collaboration has become a cornerstone for healthcare practice in recent decades resulting in the efforts at international and national levels to integrate the concept into healthcare practice and services. However, there is a paucity of research delineating strategies for professionals to apply in collaborative practice with clients in general as well as in mental health and substance abuse (MHSA) care. Methods The method applied in this paper is a form of qualitative meta-synthesis referring to the integration of findings from multiple qualitative studies within a program of research by the same investigators. Eighteen empirical papers with the focus on community MHSA practice and recovery-orientation with relevance to the service user-professional relationship in MHSA practice were included in this meta-synthesis. Results Three types of processes of collaboration specified by meta-themes were identified. The meta-themes of the interactive-dialogical process type include (a) maintaining human relationship, (b) walking alongside, (c) information sharing, (d) seizing the present moment, (e) taking the perspective of the other, and (f) aligning/scaffolding. The meta-themes of the negotiated-participatory engagement type include (a) feedback-informing process, (b) putting differences to work, (c) negotiated partnering, (d) accommodating user participation, and (e) addressing the tension between help and control. The meta-themes of the negotiated supportive process type are (a) helping in context, (b) coordinating, (c) pulling together, (d) advocating, and (e) availing. These meta-themes are strategies for collaboration applicable in MHSA practice.
Male sex is strongly associated with IgE-sensitization to airborne but not food allergens: results up to age 24 years from the BAMSE birth cohort
Authors: Melén Erik , Bergström Anna , Kull Inger , Almqvist Catarina , Andersson Niklas , Asarnoj Anna , Borres Magnus P , Georgellis Antonis , Pershagen Göran , Westman Marit , Hage Marianne van , Ballardini Natalia
Published: April 2020

Background Up to half of the population in high-income countries has allergen-specific IgE antibodies. However, data regarding sex differences of IgE-sensitization from childhood to adulthood is limited. Objective To explore IgE-sensitization to common foods and airborne allergens in relation to sex over time in a population-based birth cohort followed up to young adulthood. Methods The Swedish population-based birth cohort BAMSE includes 4,089 subjects who have been followed regularly with questionnaires and clinical investigations. A recent 24-year follow-up included 3,069 participants (75%). Sera collected at 4, 8, 16 and 24 years were analyzed for IgE-antibodies to 14 common foods and airborne allergens. Results At 24 years sensitization to foods had decreased compared to previous follow-ups affecting 8.4%, while sensitization to airborne allergens was more common, affecting 42.2%. Male sex was associated with IgE-sensitization to airborne allergens at all ages (overall OR: 1.68, 95% CI 1.46 - 1.94) while there was no statistically significant association between sex and sensitization to food allergens (overall OR: 1.10, 95% CI 0.93 - 1.32). Levels of allergen-specific IgE did not differ significantly between males and females for any of the tested foods or airborne allergens at any age, following adjustment for multiple comparisons. Conclusion IgE-sensitization to airborne allergens increases with age up to young adulthood, whereas sensitization to food allergens seems to level off. Male sex is strongly associated with IgE-sensitization to airborne allergens from early childhood up to young adulthood. In contrast, there is little evidence for associations between sex and IgE-sensitization to foods.
Prospective study of the role of HE4 and CA125 in treatment and follow-up in ovarian cancer patients
Authors: Liest Ann-Lisbeth , Rosenberg Per , Omran Ahmed Shaker , Mikiver Rasmus , Uppugunduri Srinivas
Published: April 2020

Introduction: Epithelial Ovarian Cancer, tubal- and peritoneal cancer (EOC) is still the major cause of death in gynecological cancer. The outcome of primary surgery is an important prognostic factor. The primary aim of this study was to study the utility of HE4 and CA125 in monitoring the response of chemotherapy during treatment and in predicting prognosis and recurrence during follow-up. We have also evaluated the role of HE4 as a predictor of the result of surgical intervention. Methods: Seventy-eight patients scheduled for chemotherapy were monitored with serum HE4 and CA125 during treatment and follow-up. In 39 patients samples for tumor markers were also obtained prior to surgical intervention. Results: Both HE4 and CA125 decreased in response to treatment. PFS and OS were strongly dependent on HE4 levels prior to start of chemotherapy with significantly prolonged PFS and OS when HE4 levels were under upper reference limit of 82 pmol/L (P=0.018 resp. P<0.001). The levels of HE4 correlated with primary surgical outcome with significantly lower postoperative HE4 in the radically operated group (P<0.001). An increase in HE4 and/or CA125, signals a recurrence 3-6 months before diagnosis. Median levels for both HE4 and CA125 before start, during and at the end of treatment were significantly higher for platinum resistant patients (P<0.005). Conclusion: Both tumor markers are valuable in monitoring the response of chemotherapy as well as in predicting recurrence during follow-up. Postoperative HE4 holds promise as an objective marker to evaluate the result of surgery and is highly predictive for future prognosis.
COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling
Authors: Wang Ting , Jin Haojie , Hu Jingying , Ran Haoyu , Xu Huili , Wei Lin , Gu Jianren , Qin Wenxin , Luo Xiaoying , Hao Yujun
Published: April 2020

Background: Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood. Methods: In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as its most significantly differential expression. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Relationship between COL4A1 expression and clinicopathological parameters was also analyzed. Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression. Results: COL4A1 is the most significantly overexpressed collagen gene in HCC and it closely correlates with clinical stage. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor. Conclusion: COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.
Prevalence of multimorbid degenerative lumbar spinal stenosis with knee and/or hip osteoarthritis: protocol for a systematic review and meta-analysis
Authors: Young James J. , Hartvigsen Jan , Jensen Rikke K. , Roos Ewa M. , Ammendolia Carlo , Juhl Carsten Bogh
Published: April 2020

Background: Lumbar spinal stenosis (LSS) and knee and hip osteoarthritis (OA) are prevalent conditions in the aging population and previous literature suggests they share many symptoms and are present at the same time in patients. However, no prevalence estimates of multimorbid LSS and knee and/or hip OA are currently available. The primary objective of this systematic review is therefore to estimate the prevalence of multimorbid LSS with knee and/or hip OA using radiological, clinical, and combined case definitions. Methods: This systematic review protocol has been designed according to the guidelines from the Cochrane Collaboration and are reported according the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. A comprehensive search will be performed in the following databases: MEDLINE, EMBASE, CENTRAL, and CINAHL. Web of Science will be used for forward citation tracking. No restriction in the search for publication data and language will be applied, but only articles in English will be included. The search strategy will include the following domains: LSS, knee OA, and hip OA. Retrieved citations will be screened by two authors independently. Disagreements will be discussed until consensus, or a third reviewer will be consulted if consensus cannot be reached. Data extraction and assessment of methodological quality will be done by two authors independently, using a standardized data extraction form and modified Risk of Bias Tool for Prevalence studies. Meta-analysis estimating prevalence with 95% CI will be performed using a random effects model. Meta-regression analyses will be performed to investigate the impact of LSS clinical presentations, sample population, healthcare setting, risk of bias, and other patient characteristics on prevalence estimates for multimorbid LSS and knee and/or hip OA. Discussion: The results of this review will provide the first estimates of the prevalence of multimorbid LSS and hip and knee OA based on various case definitions. The impact of covariates such as LSS clinical presentations, sample population, healthcare setting, risk of bias, and patient characteristics on prevalence estimates will also be presented. These findings will help to better understand the relationship between LSS and knee and/or hip OA and identify future research priorities. Systematic review registration: Submitted to PROSPERO, awaiting registration Keywords: Lumbar spinal stenosis, Hip osteoarthritis, Knee osteoarthritis, Multimorbidity, Prevalence, Systematic review protocol
Impact of Early Postoperative Oral Nutritional Supplement Utilization on Clinical Outcomes in Colorectal Surgery
Authors: Williams David G.A. , Ohnuma Tetsu , Krishnamoorthy Vijay , Raghunathan Karthik , Sulo Suela , Cassady Bridget A. , Hegazi Refaat , Wischmeyer Paul E.
Published: April 2020

Background: Small randomized trials of early postoperative oral nutritional supplementation (ONS) suggest various health benefits following colorectal surgery (CRS). However, real-world evidence of the impact of early ONS on clinical outcomes in CRS is lacking.Methods: Using a nationwide administrative-financial database (Premier Healthcare Database), we examined the association between early ONS use and postoperative clinical outcomes in patients undergoing elective open or laparoscopic CRS between 2008–2014. Early ONS was defined as the presence of charges for ONS before postoperative day (POD) 3. The primary outcome was composite infectious complications. Key secondary efficacy (intensive care unit (ICU) admission and gastrointestinal complications) and falsification (blood transfusion and myocardial infarction) outcomes were also examined. Propensity score matching was used to assemble patient groups that were comparable at baseline and differences in outcomes were examined.Results: Overall, patients receiving early ONS were older with greater comorbidities, and more likely to be Medicare beneficiaries with malnutrition. In a well-matched sample of early-ONS recipients (n=267) versus non-recipients (n= 534), infectious complications were significantly lower in early-ONS recipients (6.7% vs. 11.8%, P<0.03). Early-ONS use was also associated with significantly reduced rates of pneumonia (P<0.04), ICU admissions (P<0.04), and gastrointestinal complications (P<0.05). There were no significant differences in falsification outcomes. Conclusions: Although early postoperative ONS after CRS was more likely to be utilized in elderly patients with greater comorbidities, use of early ONS was associated with reduced infectious complications, pneumonia, ICU admission, and gastrointestinal complications. This propensity-score matched study using real-world data suggests that clinical outcomes are improved with early ONS use, a simple and inexpensive intervention in CRS patients.
A Cluster Randomized Trial of Delivery of Intermittent Preventive Treatment of Malaria in Pregnancy at the Community Level in Burkina Faso
Authors: Gutman Julie , Stephens Daniel K , Tiendrebeogo Justin , Badolo Ousmane , Dodo Mathurin , Burke Danielle , Williamson John , Vibbert Kristen , Youll Susan J , Savadogo Yacouba , Brieger William R.
Published: April 2020

Background: Malaria in pregnancy is responsible for 8–14% of low birth weight and 20% of stillbirths in sub-Saharan Africa. To prevent these adverse consequences, the World Health Organization recommends intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine be administered at each ANC visit starting as early as possible in the second trimester. Global IPTp coverage in targeted countries remains unacceptably low. Community delivery of IPTp was explored as a means to improve coverage. Methods: A cluster randomized, controlled trial was conducted in 12 health facilities in a 1:1 ratio to either an intervention group (IPTp delivered by CHWs) or a control group (standard practice, with IPTp delivered at HFs) in three districts of Burkina Faso to assess the effect of IPTp administration by community health workers (CHWs) on the coverage of IPTp and antenatal care (ANC). The districts and facilities were purposively selected taking into account malaria epidemiology, IPTp coverage, and the presence of active CHWs. Pre- and post-intervention surveys were carried out in March 2017 and July–August 2018, respectively. A difference in differences (DiD) analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. Results: Altogether 374 and 360 women were included in the baseline and endline surveys, respectively. At baseline, women received a median of 2.1 doses; by endline, women received a median of 1.8 doses in the control group and 2.8 doses in the intervention group (p-value <.0001). There was a non-statistically significant increase in the proportion of women attending four ANC visits in the intervention compared to control group (DiD= 12.6%, p-value= 0.16). By the endline, administration of IPTp was higher in the intervention than control, with a DiD of 17.6% for IPTp3 (95% confidence interval (CI) -16.3, 51.5; p-value 0.31) and 20.0% for IPTp4 (95% CI -7.2, 47.3; p-value= 0.15). Conclusions: Community delivery of IPTp could potentially lead to a greater number of IPTp doses delivered, with no apparent decrease in ANC coverage.
The Genetic Regulation of size Variation in the Transcriptome of the Cerebrum in the Chicken and its role in domestication and brain size evolution
Authors: Höglund Andrey , Strempfl katharina , Fogelholm Jesper , Wright Dominic , Henriksen Rie
Published: April 2020

Background: Large difference in cerebrum size exist between avian species and populations of the same species and is believed to reflect differences in processing power. During domestication chickens developed a larger cerebrum compared to their wild progeny, the Red Jungle fowl. The underlying mechanisms that control cerebrum size and the extent to which genetic regulation is similar across brain regions is not well understood. In this study, we combine measurement of cerebrum size with genome-wide genetical genomics analysis to identify the genetic architecture of the cerebrum, as well as compare the regulation of gene expression in this brain region with gene-expression in other regions of the brain (the hypothalamus) and somatic tissue (liver). Results: We identify one candidate gene that putatively regulates cerebrum size ( MTF2 ) as well as identified a large number of eQTL that regulate the transcriptome in cerebrum tissue, with the majority of these eQTL being trans-acting. The overall regulation of gene expression variation in the cerebrum was markedly different to the hypothalamus, with relatively few eQTL in common. In comparison, the cerebrum tissue shared more eQTL with a distant tissue (liver) than with a neighboring tissue (hypothalamus). Conclusion: The candidate gene for cerebrum size ( MTF2 ) has previously been linked to brain development making it a good candidate for further investigation as a regulator of inter-population variation in cerebrum size. The lack of shared eQTL between the two brain regions implies that genetic regulation of gene expression appears to be relatively independent between the two brain regions and suggest that co-evolution between these two brain regions might be more functionally driven than developmental. These findings have relevance for current brain size evolution theories.