bluuebunny/crossref_metadata_2025 huggingface dataset:
Structured headache services as the solution to the ill-health burden of headache. 2. Modelling effectiveness and cost-effectiveness of implementation in Europe: methodology
Authors: Tinelli Michela , Leonardi Matilde , Paemeleire Koen , Mitsikostas Dimos , de la Torre Elena Ruiz , Steiner Timothy J. ,   on behalf of the European Brain Council Value of Treatment Headache Working Group, the European Headache Federation, the European Federation of Neurological Associations, and Lifting The Burden: the Global Campaign against Headache
Published: August 2021

Background

Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council’s Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache.

Methods

We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros).

Results

The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere.

Conclusions

This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations.
Whole genome sequence based capsular typing and antimicrobial resistance prediction of Group B streptococcal isolates from colonized pregnant women in Nigeria
Authors: Bob-Manuel Mienye , McGee Lesley , Igunma Jeremiah A , Alex-Wele Mary A , Obunge Orikomaba K , Wariso Kennedy T
Published: August 2021

Background

Streptococcus agalactiae (Group B Streptococcus, GBS) is one of the major bacterial pathogens responsible for neonatal sepsis. Whole genome sequencing has, in recent years, emerged as a reliable tool for capsular typing and antimicrobial resistance prediction. This study characterized vaginal and rectal isolates of Group B Streptococcus obtained from pregnant women in Port Harcourt, Nigeria using a whole-genome sequence-based approach.

Results

Capsular types Ia, Ib, II, III, IV and V were detected among the 43 isolates sequenced. Twelve sequence types (STs) were identified, with ST19 (n = 9, 27.3 %) and ST486 (n = 5, 15.2 %) the most frequent among non-duplicated isolates. Of the alpha-like proteins (alp) identified, Alp1 was the most prevalent in 11 (33.3 %) isolates. Macrolide and lincosamide resistance determinants were present in 15 (45.5 %) isolates; ermB was detected in 1 (3 %), ermTR in 7 (21.2 %) isolates, lnu gene was detected in 6 (18.2 %) and mef was identified in 3 (9.1 %) isolates. Resistance of GBS to erythromycin and clindamycin (predicted from presence of erm or mef genes) was found to be 30.3 % and 24.2 %, respectively. All isolates were predicted resistant to tetracycline with only the tetM gene identified. Fluoroquinolone-resistance conferring substitutions in gyrA + parC were detected in 9 (27.3 %) isolates and chloramphenicol resistance was predicted from presence of aac6’-aph2 gene in 11 (33.3 %).

Conclusions

The data available from the whole genome sequencing of these isolates offers a small but insightful description of common serotypes and resistance features within colonizing GBS in Nigeria.
Comparative phylogenetic analysis of CBL reveals the gene family evolution and functional divergence in Saccharum spontaneum
Authors: Feng Xiaomin , Wang Yongjun , Zhang Nannan , Gao Shuai , Wu Jiayun , Liu Rui , Huang Yonghong , Zhang Jisen , Qi Yongwen
Published: August 2021

Background

The identification and functional analysis of genes that improve tolerance to low potassium stress in S. spontaneum is crucial for breeding sugarcane cultivars with efficient potassium utilization. Calcineurin B-like (CBL) protein is a calcium sensor that interacts with specific CBL-interacting protein kinases (CIPKs) upon plants’ exposure to various abiotic stresses.

Results

In this study, nine CBL genes were identified from S. spontaneum. Phylogenetic analysis of 113 CBLs from 13 representative plants showed gene expansion and strong purifying selection in the CBL family. Analysis of CBL expression patterns revealed that SsCBL01 was the most commonly expressed gene in various tissues at different developmental stages. Expression analysis of SsCBLs under low K+ stress indicated that potassium deficiency moderately altered the transcription of SsCBLs. Subcellular localization showed that SsCBL01 is a plasma membrane protein and heterologous expression in yeast suggested that, while SsCBL01 alone could not absorb K+, it positively regulated K+ absorption mediated by the potassium transporter SsHAK1.

Conclusions

This study provided insights into the evolution of the CBL gene family and preliminarily demonstrated that the plasma membrane protein SsCBL01 was involved in the response to low K+ stress in S. spontaneum.
Older women’s experiences of companion animal death: impacts on well-being and aging-in-place
Authors: Wilson Donna M , Underwood Leah , Carr Eloise , Gross Douglas P , Kane Morgan , Miciak Maxi , Wallace Jean E , Brown Cary A
Published: August 2021

Background

Companion animal death is a common source of grief, although the extent and context of that grief is poorly understood, especially in older adulthood. The aim of this multiple-methods study was to develop a greater understanding of the impact of companion animal death on older women living alone in the community, as older women are a distinct at-risk group, and the supports that should be available to help these individuals with their grief.

Methods

Participants were recruited from across Alberta, a Canadian province, through seniors’ organizations, pet rescue groups, and social media groups of interest to older women. After completing a pre-interview online questionnaire to gain demographic information and standardized pet attachment and grief measures data, participants were interviewed through the Zoom ® computer program or over the telephone. An interpretive description methodology framed the interviews, with Braun and Clarke’s 6-phase analytic method used for thematic analysis of interview data.

Results

In 2020, twelve participants completed the pre-interview questionnaires and nine went on to provide interview data for analysis. All were older adult (age 55+) women, living alone in the community, who had experienced the death of a companion animal in 2019. On the standardized measures, participants scored highly on attachment and loss, but low on guilt and anger. The interview data revealed three themes: catastrophic grief and multiple major losses over the death of their companion animal, immediate steps taken for recovery, and longer-term grief and loss recovery.

Conclusions

The findings highlight the importance of acknowledging and addressing companion animal grief to ensure the ongoing well-being and thus the sustained successful aging-in-place of older adult women in the community.
Protocol for an interventional study to reduce postpartum weight retention in obese mothers using the internet of things and a mobile application: a randomized controlled trial (SpringMom)
Authors: Kawasaki Maki , Mito Asako , Waguri Masako , Sato Yuichi , Abe Emiko , Shimada Mayumi , Fukuda Sayuri , Sasaki Yuki , Fujikawa Kei , Sugiyama Takashi , Ota Erika , Nakazawa Jin , Okoshi Tadashi , Takimoto Hidemi , Honda Yuka , Inoue Eisuke , Hiramatsu Yuji , Arata Naoko
Published: August 2021

Background

Obese pregnant women are known to experience poorer pregnancy outcomes and are at higher risk of postnatal arteriosclerosis. Hence, weight control during and after pregnancy is important for reducing these risks. The objective of our planned randomized controlled trial is to evaluate whether the rate of change in body weight in obese women before pregnancy to 12 months postpartum would be lower with the use of an intervention consisting of Internet of Things (IoT) devices and mobile applications during pregnancy to 1 year postpartum compared to a non-intervention group.

Methods

Women will be recruited during outpatient maternity checkups at four perinatal care institutions in Japan. We will recruit women at less than 30 weeks of gestation with a pre-pregnancy body mass index ≥ 25 kg/m2. The women will be randomly assigned to an intervention or non-intervention group. The intervention will involve using data (weight, body composition, activity, sleep) measured with IoT devices (weight and body composition monitor, activity, and sleep tracker), meal records, and photographs acquired using a mobile application to automatically generate advice, alongside the use of a mobile application to provide articles and videos related to obesity and pregnancy. The primary outcome will be the ratio of change in body weight (%) from pre-pregnancy to 12 months postpartum compared to before pregnancy.

Discussion

This study will examine whether behavioral changes occurring during pregnancy, a period that provides a good opportunity to reexamine one's habits, lead to lifestyle improvements during the busy postpartum period. We aim to determine whether a lifestyle intervention that is initiated during pregnancy can suppress weight gain during pregnancy and encourage weight loss after delivery.

Trial registration

UMIN: UMIN (University hospital Medical Information Network) 000,041,460. Resisted on 18th August 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047278
Factors influencing haze formation and corneal flattening, and the impact of haze on visual acuity after conventional collagen cross-linking: a 12-month retrospective study
Authors: Csorba Anita , Kránitz Kinga , Dormán Péter , Popper-Sachetti Andrea , Kiss Huba , Szalai Irén , Nagy Zoltán Zsolt
Published: August 2021

Background

Our aim was to determine associations of pachymetry, keratometry, and their changes with haze formation and corneal flattening after collagen cross-linking, and to analyse the relationship between postoperative haze and visual outcome.

Methods

Retrospective analysis was performed on 47 eyes of 47 patients with keratoconus using the Pentacam HR Scheimpflug camera before and 1, 3, 6 and 12 months after cross-linking. Corneal backscattered light values in grey scale unit were recorded in the anterior, center and posterior corneal layers and in four concentric rings. Surface area- and thickness-corrected grey scale unit values were assessed with an additional calculation. Friedman test with post hoc Wilcoxon signed-rank test was used to analyse changes in visual acuity, pachymetry, keratometry and densitometry. Spearman’s rank correlation test was used to detect correlations of haze formation and corneal flattening with pachymetry, keratometry and their postoperative change. Generalized estimating equations analysis was used to investigate the influence of densitometry values on postoperative visual acuity after controlling for the effect of preoperative keratometry.

Results

One year after treatment, significant flattening was observed in maximum and mean keratometry readings (p < 0.001). Significantly increased densitometry values were observed in three central rings compared to baseline (post hoc p < 0.0125). According to receiver operating characteristic curve, densitometry value of the anterior layer of 0–2 mm ring was the most characteristic parameter of densitometry changes after cross-linking (area under the curve = 0.936). Changes in haze significantly correlated with preoperative maximum keratometry (R = 0.303, p = 0.038) and with the changes in maximum keratometry (R = -0.412, p = 0.004). Changes in maximum keratometry correlated with preoperative maximum keratometry (R = -0.302, p = 0.038). Postoperative haze had a significant impact on uncorrected and best corrected distance visual acuity (β coefficient = 0.006, p = 0.041 and β coefficient = 0.003, p = 0.039, respectively).

Conclusions

Our findings indicate that in more advanced keratoconus more significant corneal flattening effect parallel with haze formation can be observed after cross-linking. Despite significant reduction of keratometry, postoperative corneal haze may limit final visual acuity.
Coronary artery calcium in patients with schizophrenia
Authors: Trab Trine , Attar Rubina , Jensen Svend Eggert , Grøntved Simon , Frøkjær Jens Brøndum , Polcwiartek Christoffer , Nielsen René Ernst
Published: August 2021

Background

Coronary heart disease (CHD) is a major cause of increased mortality rates in patients with schizophrenia. Moreover, coronary artery calcium (CAC) score is associated with CHD. We hypothesized that patients with schizophrenia have more CAC than the general population and aimed to investigate the CAC score in patients with schizophrenia compared to norms based on the general population. Additionally, this study investigated if age, sex, diabetes, dyslipidemia and smoking were associated with the CAC score.

Methods

In a cross-sectional study, 163 patients with schizophrenia underwent cardiac computed tomography, and the CAC score was measured and compared to norms by classifying the CAC scores in relation to the age- and gender matched norm 50th, 75th and 90th percentiles. Logistic and linear regression were carried out to investigate explanatory variables for the presence and extent of CAC, respectively.

Results

A total of 127 (77.9%) patients had a CAC score below or equal to the matched 50th, 20 (12.3%) above the 75th and nine (5.5%) above the 90th percentile. Male sex (P < 0.05), age (P < 0.001) and smoking (P < 0.05) were associated with the presence of CAC while age (P < 0.001) and diabetes (P < 0.01) were associated with the extent of CAC.

Conclusions

The amount of CAC in patients with schizophrenia follows norm percentiles, and variables associated with the CAC score are similar in patients with schizophrenia and the general population. These findings indicate that the CAC score may not be sufficient to detect the risk of CHD in patients with schizophrenia. Future studies should explore other measures of subclinical CHD, including measures of peripheral atherosclerosis or cardiac autonomic neuropathy to improve early detection and intervention.

Trial registration

ClinicalTrials.gov Identifier: NCT02885792, September 1, 2016.
Covid-19 pandemic impact on maternal and child health services access in Nampula, Mozambique: a mixed methods research
Authors: das Neves Martins Pires Paulo Henrique , Macaringue Cynthia , Abdirazak Ahmed , Mucufo Jaibo Rassul , Mupueleque Martins Abudo , Zakus David , Siemens Ronald , Belo Celso Fernando
Published: August 2021

Background

The Covid-19 pandemic has so far infected more than 30 million people in the world, having major impact on global health with collateral damage. In Mozambique, a public state of emergency was declared at the end of March 2020. This has limited people’s movements and reduced public services, leading to a decrease in the number of people accessing health care facilities. An implementation research project, The Alert Community for a Prepared Hospital, has been promoting access to maternal and child health care, in Natikiri, Nampula, for the last four years. Nampula has the second highest incidence of Covid-19. The purpose of this study is to assess the impact of Covid-19 pandemic Government restrictions on access to maternal and child healthcare services. We compared health centres in Nampula city with healthcare centres in our research catchment area. We wanted to see if our previous research interventions have led to a more resilient response from the community.

Methods

Mixed-methods research, descriptive, cross-sectional, retrospective, using a review of patient visit documentation. We compared maternal and child health care unit statistical indicators from March–May 2019 to the same time-period in 2020. We tested for significant changes in access to maternal and child health services, using KrushKall Wallis, One-way Anova and mean and standard deviation tests.

We compared interviews with health professionals, traditional birth attendants and patients in the two areas. We gathered data from a comparable city health centre and the main city referral hospital. The Marrere health centre and Marrere General Hospital were the two Alert Community for a Prepared Hospital intervention sites.

Results

Comparing 2019 quantitative maternal health services access indicators with those from 2020, showed decreases in most important indicators: family planning visits and elective C-sections dropped 28%; first antenatal visit occurring in the first trimester dropped 26%; hospital deliveries dropped a statistically significant 4% (p = 0.046), while home deliveries rose 74%; children vaccinated down 20%.

Conclusion

Our results demonstrated the negative collateral effects of Covid-19 pandemic Government restrictions, on access to maternal and child healthcare services, and highlighted the need to improve the health information system in Mozambique.
Increased habitual flavonoid intake predicts attenuation of cognitive ageing in twins
Authors: Jennings Amy , Steves Claire J. , Macgregor Alexander , Spector Tim , Cassidy Aedín
Published: August 2021

Background

Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods.

Methods

We aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18–89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors.

Results

Higher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77;p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81;p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21;p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24;p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= −0.52, 95% CI 0.19, 0.84;p=0.001) and with faster simple reaction times (T3-T1= −18.1, 95% CI −35.4, −0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%,p=0.01) and proanthocyanidin (2.0%,p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years.

Conclusion

Small increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing.
Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme
Authors: Chkioua Latifa , Amri Yessine , Chaima Sahli , Fenni Ferdawes , Boudabous Hela , Ben Turkia Hadhami , Messaoud Taieb , Tebib Neji , Laradi Sandrine
Published: August 2021

Background

Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-l-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex.

Methods

All exons and flanking intron regions of FUCA1 were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with fucosidosis. Bioinformatics tools were then used to predict the impacts of novel alterations on the structure and function of proteins. Furthermore, the identified mutations were localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software, which established a function-structure relationship of the FUCA1 proteins.

Results

Four novel mutations were identified in this study. Two patients (P1 and P2) in Families 1 and 2 who had the severe phenotype were homoallelic for the two identified frameshift mutations p.K57Sfs*75 and p.F77Sfs*55, respectively. The affected patient (P3) from Family 3, who had the milder phenotype, was heterozygous for the novel missense mutation p.G332E and the novel splice site mutation c.662+5g>c. We verified that this sequence variation did not correspond to a polymorphism by testing 50 unrelated individuals. Additionally, 16 FUCA1 polymorphisms were identified. The structure prediction analysis showed that the missense mutation p.G332E would probably lead to a significant conformational change, thereby preventing the expression of the FUCA1 protein indeed; the 3D structural model of the FUCA1 protein reveals that the glycine at position 332 is located near a catalytic nucleophilic residue. This makes it likely that the enzymatic function of the protein with p.G332E is severely impaired.

Conclusion

These are the first FUCA1 mutations identified in Tunisia that cause the fucosidosis disease. Bioinformatics analysis allowed us to establish an approximate structure–function relationship for the FUCA1 protein, thereby providing better genotype/phenotype correlation knowledge.
Genetic diversity and epidemiology of human rhinovirus among children with severe acute respiratory tract infection in Guangzhou, China
Authors: Li Wanwei , Yu Bo , Zhou Jijian , Wang Yanlan , Xue Bao , Pan Jialong , Ran Yanhong , Yang Xiaoping , Wang Xiaoping , Yang Fang , Li Hongjian
Published: August 2021

Background

Human rhinovirus (HRV) is one of the major viruses of acute respiratory tract disease among infants and young children. This work aimed to understand the epidemiological and phylogenetic features of HRV in Guangzhou, China. In addition, the clinical characteristics of hospitalized children infected with different subtype of HRV was investigated.

Methods

Hospitalized children aged < 14 years old with acute respiratory tract infections were enrolled from August 2018 to December 2019. HRV was screened for by a real-time reverse-transcription PCR targeting the viral 5′UTR.

Results

HRV was detected in 6.41% of the 655 specimens. HRV infection was frequently observed in children under 2 years old (57.13%). HRV-A and HRV-C were detected in 18 (45%) and 22 (55%) specimens. All 40 HRV strains detected were classified into 29 genotypes. The molecular evolutionary rate of HRV-C was estimated to be 3.34 × 10–3 substitutions/site/year and was faster than HRV-A (7.79 × 10–4 substitutions/site/year). Children who experienced rhinorrhoea were more common in the HRV-C infection patients than HRV-A. The viral load was higher in HRV-C detection group than HRV-A detection group (p = 0.0148). The median peak symptom score was higher in patients with HRV-C infection as compared to HRV-A (p = 0.0543), even though the difference did not significance.

Conclusion

This study revealed the molecular epidemiological characteristics of HRV in patients with respiratory infections in southern China. Children infected with HRV-C caused more severe disease characteristics than HRV-A, which might be connected with higher viral load in patients infected with HRV-C. These findings will provide valuable information for the pathogenic mechanism and treatment of HRV infection.
Safe by design (SbD) and nanotechnology: a much-discussed topic with a prudence?
Authors: Gulumian Mary , Cassee Flemming R.
Published: August 2021

Safe-by-Design (SbD) has been put forward as a concept to assure that only safe nanomaterials will reach the market and that safety aspects have already been considered in a very early stage of the innovation process. In practice, several laboratory test have been proposed to screen newly developed nanomaterials and nano-enabled products to assess their hazardous nature. These tests need to have sufficient predictive power for possible adverse effects on human health, not only due to acute (peak) exposures, but also for long-term (low dose) exposures as these materials may accumulate over time in organs and tissues.
Effect of osteoporotic conditions on the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma
Authors: Kang Sang Mook , Kim Jae Min , Cheong Jin Hwan , Ryu Je Il , Won Yu Deok , Kim Young Soo , Han Myung-Hoon
Published: August 2021

Purpose

Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma.

Methods

A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation.

Results

A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037).

Conclusions

Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made.

Graphic abstract
Comprehensive analysis of metabolism-related lncRNAs related to the progression and prognosis in osteosarcoma from TCGA
Authors: Chen Xingyin , Ye Zhengyun , Lou Pan , Liu Wei , Liu Ying
Published: August 2021

Background

Osteosarcoma is one of the most common malignant neoplasms in children and adolescents. Studies have shown that metabolism-related pathways are vital for the development and metastasis of osteosarcoma. Long non-coding RNA (lncRNA) plays a key role in the occurrence and progression of cancer in a variety of ways. However, the detailed molecular mechanisms of metabolism-related lncRNA in osteosarcoma remain to be deeply elucidated.

Methods

In this study, all metabolism-related mRNAs and lncRNAs in osteosarcoma were extracted and identified based on transcriptomic data from the TCGA database. Usingsurvival analysis, univariate and multivariate independent prognostic analysis, gene set enrichment analysis, and nomogram, a prognostic signature with metabolic lncRNAs as prognostic factors was constructed.

Results

Nine prognostic factors included lncRNA AC009779.2, lncRNA AL591895.1, lncRNA AC026271.3, lncRNA LPP-AS2, lncRNA LINC01857, lncRNA AP005264.1, lncRNA LINC02454, lncRNA AL133338.1, and lncRNA AC135178.5, respectively. Survival analysis indicated that alterations of specific lncRNA expression were strongly correlated with poor prognosis in osteosarcoma. Univariate and multivariate independent prognostic analysis showed that the prognostic signature had a good independent predictive ability for patient survival. The results of GSEA suggested that these predictors may be involved in the metabolism of certain substances or energy in cancer. The nomogram was further drawn for clinical guidance and assistance in clinical decision-making.

Conclusions

This study identified multiple metabolism-related lncRNAs, which may be novel therapeutic targets for osteosarcoma, and contributed to better explore the specific metabolic regulatory mechanisms of lncRNA in osteosarcoma.
Investigation of timing of surgery and other factors possibly influencing outcome in dogs with acute thoracolumbar disc extrusion: a retrospective study of 1501 cases
Authors: Immekeppel Almut , Rupp Stefan , Demierre Stanislas , Rentmeister Kai , Meyer-Lindenberg Andrea , Goessmann Julia , Bali Monty Siddartha , Schmidli-Davies Fenella , Forterre Franck
Published: August 2021

Background

Intervertebral disc extrusions in the thoracolumbar region are a common spinal neurologic disorder in dogs and usually considered a neurological emergency. Several factors, like timing of surgery, have previously been analysed in order to determine the effect on outcome and time of recovery. Most studies have investigated one defined population of dogs and the influence of a single factor on the overall outcome. In this retrospective study, a large cohort of dogs and the influence of one or combinations of several factors on outcome and time of recovery were analysed.

Results

The bivariate analysis demonstrated a significant association between the following variables and the time of recovery: the time span between the onset of clinical signs and surgery (Cramers Phi $$\varphi^{\prime}$$

φ
′

 = 0.14; P = 0.003), the grade of severity ($$\varphi^{\prime}$$

φ
′

 = 0.23; P < 0.001) and the implementation of physical rehabilitation ($$\varphi^{\prime}$$

φ
′

 = 0.2; P < 0.001). However, the analysis of a multivariable regression model demonstrated that a significant correlation only exists between the time span between the onset of clinical signs and surgery and the overall outcome (P = 0.007), as well as between the grade of severity and the time of recovery (P < 0.001). The percentage of dogs with lacking deep pain perception (DPP) that had to be euthanised due to their neurological condition, decreased from 20.0 to 2.9% when physical rehabilitation was implemented. Additionally, the proportion of dogs (same group) that improved to reach an ambulatory status increased from 80.0 to 91.4%.

Conclusion

The results of the bivariate analysis demonstrated several correlations between some variables and overall outcome or time of recovery, whereas the multivariable regression model demonstrated only two associations. The time span between the onset of clinical signs and surgery was significantly associated with the overall outcome. We therefore suggest that a surgical intervention should be performed without unreasonable delay. Due to the correlation between the grade of severity and time of recovery, owners of dogs with more severe neurological deficits prior to surgery should be informed about the presumably prolonged time of recovery.
Phase 1 clinical trial of the PI3Kδ inhibitor YY-20394 in patients with B-cell hematological malignancies
Authors: Jiang Bo , Qi Junyuan , Song Yuqin , Li Zengjun , Tu Meifeng , Ping Lingyan , Liu Zongliang , Bao Hanying , Xu Zusheng , Qiu Lugui
Published: August 2021

YY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20–200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted.

Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1.
Incidence of delayed bleeding in patients on antiplatelet therapy after mild traumatic brain injury: a systematic review and meta-analysis
Authors: Colombo Giorgio , Bonzi Mattia , Fiorelli Elisa , Jachetti Alessandro , Bozzano Viviana , Casazza Giovanni , Solbiati Monica , Costantino Giorgio
Published: August 2021

Background

The scientific evidence regarding the risk of delayed intracranial bleeding (DB) after mild traumatic brain injury (MTBI) in patients administered an antiplatelet agent (APA) is scant and incomplete. In addition, no consensus exists on the utility of a routine repeated head computed tomography (CT) scan in these patients.

Objective

The aim of this study was to evaluate the risk of DB after MTBI in patients administered an APA.

Methods

A systematic review and meta-analysis of prospective and retrospective observational studies enrolling adult patients with MTBI administered an APA and who had a second CT scan performed or a clinical follow-up to detect any DB after a first negative head CT scan were conducted. The primary outcome was the risk of DB in MTBI patients administered an APA. The secondary outcome was the risk of clinically relevant DB (defined as any DB leading to neurosurgical intervention or death).

Results

Sixteen studies comprising 2930 patients were included in this meta-analysis. The pooled absolute risk for DB was 0.77% (95% CI 0.23–1.52%), ranging from 0 to 4%, with substantial heterogeneity (I2 = 61%). The pooled incidence of clinically relevant DB was 0.18%. The subgroup of patients on dual antiplatelet therapy (DAPT) had an increased DB risk, compared to the acetylsalicylic acid (ASA)-only patients (2.64% vs. 0.22%; p = 0.04).

Conclusion

Our systematic review showed a very low risk of DB in MTBI patients on antiplatelet therapy. We believe that such a low rate of DB could not justify routine repeated CT scans in MTBI patients administered a single APA. We speculate that in the case of clinically stable patients, a repeated head CT scan could be useful for select high-risk patients and for patients on DAPT before discharge.
Composition analysis and microencapsulation of Eucommia ulmoides seed oil
Authors: Huirong Zhang , huina Zhang , Nifeng Chen , Li Li
Published: August 2021

Background

Eucommia ulmoides seed oil is a functional health oil with a high content of unsaturated fatty acids. However, excessively high content of unsaturated fatty acids can cause E. ulmoides seed oil to easily spoil. Microencapsulation technology can effectively encapsulate substances, thereby prolonging the spoilage time of oil products.

Methods

In the present study, E. ulmoides seed oil from different manufacturers were analyzed by Agilent 7890B-5977A gas chromatography–mass spectrometry. Encapsulation efficiency, yield rate, and scanning electron microscopy results between microcapsules prepared use different wall materials and different methods (spray drying and complex coagulation) were compared to determine the best preparation process for microcapsules. The Wantong 892 professional oil oxidation stability tester was used to measure the induced oxidation time of the E. ulmoides seed oil and microcapsules.

Conclusion

E. ulmoides seed oil comprises > 80% unsaturated fatty acids with a high α-linolenic acid content, followed by linoleic acid. The most promising combination was chitosan:gum arabic at 1:8 as the wall material and complex coagulation. The best preparation had a wall material concentration, stirring speed, aggregation pH, and core-to-wall ratio of 2.5%, 500 rpm, 4.2, and 1:4, respectively. Microcapsules prepared under these conditions exhibited higher yield and encapsulation efficiency (94.0% and 73.3%, respectively). The induced oxidation time of the E. ulmoides seed oil and microcapsules were 3.8 h and 13.9 h, respectively, indicating that microencapsulation can increase the oxidation induction time of this oil.
Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9
Authors: Briggs Erica M. , Mita Paolo , Sun Xiaoji , Ha Susan , Vasilyev Nikita , Leopold Zev R. , Nudler Evgeny , Boeke Jef D. , Logan Susan K.
Published: August 2021

Background

The autonomous retroelement Long Interspersed Element-1 (LINE-1) mobilizes though a copy and paste mechanism using an RNA intermediate (retrotransposition). Throughout human evolution, around 500,000 LINE-1 sequences have accumulated in the genome. Most of these sequences belong to ancestral LINE-1 subfamilies, including L1PA2-L1PA7, and can no longer mobilize. Only a small fraction of LINE-1 sequences, approximately 80 to 100 copies belonging to the L1Hs subfamily, are complete and still capable of retrotransposition. While silenced in most cells, many questions remain regarding LINE-1 dysregulation in cancer cells.

Results

Here, we optimized CRISPR Cas9 gRNAs to specifically target the regulatory sequence of the L1Hs 5’UTR promoter. We identified three gRNAs that were more specific to L1Hs, with limited binding to older LINE-1 sequences (L1PA2-L1PA7). We also adapted the C-BERST method (dCas9-APEX2 Biotinylation at genomic Elements by Restricted Spatial Tagging) to identify LINE-1 transcriptional regulators in cancer cells. Our LINE-1 C-BERST screen revealed both known and novel LINE-1 transcriptional regulators, including CTCF, YY1 and DUSP1.

Conclusion

Our optimization and evaluation of gRNA specificity and application of the C-BERST method creates a tool for studying the regulatory mechanisms of LINE-1 in cancer. Further, we identified the dual specificity protein phosphatase, DUSP1, as a novel regulator of LINE-1 transcription.
Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain
Authors: Legault L. M. , Doiron K. , Breton-Larrivée M. , Langford-Avelar A. , Lemieux A. , Caron M. , Jerome-Majewska L. A. , Sinnett D. , McGraw S.
Published: August 2021

Background

Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology.  However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program.

Results

Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development).

Conclusion

These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.
Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD
Authors: Vijverberg E. G. B. , Axelsen T. M. , Bihlet A. R. , Henriksen K. , Weber F. , Fuchs K. , Harrison J. E. , Kühn-Wache K. , Alexandersen P. , Prins N. D. , Scheltens Philip
Published: August 2021

Background

Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD.

Methods

This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics.

Results

To be expected early 2023

Conclusion

This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta.

Trial registration

ClinicalTrials.gov Identifier: NCT04498650
Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application
Authors: Zhao Yunyu , Yan Zhipeng , Liu Ying , Zhang Yue , Shi Jie , Li Jingtao , Ji Fanpu
Published: August 2021

Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.
Generalized fuzzy GV-Hausdorff distance in GFGV-fractal spaces with application in integral equation
Authors: Alihajimohammad Alireza , Saadati Reza
Published: August 2021

We propose a method for constructing a generalized fuzzy Hausdorff distance on the set of the nonempty compact subsets of a given generalized fuzzy metric space in the sence of George–Veeramni and Tian–Ha–Tian. Next, we define the generalized fuzzy fractal spaces. Morever, we obtain a fixed point theorem of a class of generalized fuzzy contractions and present an application in integranl equation.
Inequalities for generalized Riemann–Liouville fractional integrals of generalized strongly convex functions
Authors: Farid Ghulam , Kwun Young Chel , Yasmeen Hafsa , Akkurt Abdullah , Kang Shin Min
Published: August 2021

Some new integral inequalities for strongly $(\alpha ,h-m)$
(
α
,
h
−
m
)
-convex functions via generalized Riemann–Liouville fractional integrals are established. The outcomes of this paper provide refinements of some fractional integral inequalities for strongly convex, strongly m-convex, strongly $(\alpha ,m)$
(
α
,
m
)
-convex, and strongly $(h-m)$
(
h
−
m
)
-convex functions. Also, the refinements of error estimations of these inequalities are obtained by using two fractional integral identities. Moreover, using a parameter substitution and a constant multiplier, k-fractional versions of established inequalities are also given.