bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk
Authors: Jordahl Kristina M. , Phipps Amanda I. , Randolph Timothy W. , Tinker Lesley F. , Nassir Rami , Hou Lifang , Anderson Garnet L. , Kelsey Karl T. , White Emily , Bhatti Parveen
Published: November 2020

Background

Though bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL).

Methods

Among 412 bladder cancer cases and 424 controls from the Women’s Health Initiative (WHI), we assessed whether the effects of these SNPs on bladder cancer are mediated through proximal DNA methylation changes in pre-diagnostic blood at mQTL-associated CpG sites, which we refer to as natural indirect effects (NIEs). We used a multiple-mediator mediation model for each of the four mQTL adjusted for matching variables and potential confounders, including race/ethnicity, smoking status, and pack-years of smoking.

Results

While not statistically significant, our results suggest that substantial proportions of the modest effects of rs401681 (ORNIE = 1.05, 95% confidence interval (CI) = 0.89 to 1.25; NIE percent = 98.5%) and rs2294008 (ORNIE = 1.10, 95% CI = 0.90 to 1.33; NIE percent = 77.6%) on bladder cancer risk are mediated through differential DNA methylation at nearby mQTL-associated CpG sites. The suggestive results indicate that rs2294008 may affect bladder cancer risk through a set of genes in the lymphocyte antigen 6 family, which involves genes that bind to and modulate nicotinic acetylcholine receptors. There was no suggestive evidence supporting mediation for rs8102137 and rs798766.

Conclusions

Though larger studies are necessary, the methylation changes associated with rs401681 and rs2294008 at mQTL-associated CpG sites may be relevant for bladder carcinogenesis, and this study demonstrates how multi-omic data can be integrated to help understand the downstream effects of genetics variants.
Overwhelming sepsis in a neonate affected by Zellweger syndrome due to a compound heterozygosis in PEX 6 gene: a case report
Authors: Lucaccioni Laura , Righi Beatrice , Cingolani Greta Miriam , Lugli Licia , Della Casa Elisa , Torcetta Francesco , Iughetti Lorenzo , Berardi Alberto
Published: November 2020

Background

Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period.

Case presentation

A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test.

Conclusions

ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.
Intracranial hypertension due to spinal cord tumor misdiagnosed as pseudotumor cerebri syndrome: case report
Authors: Hu Wanglu , Wang Chun , Wu Qun , Chen Yike , Gao Wei , Ying Guangyu , Zhu Yongjian , Yan Wei
Published: November 2020

Background

Isolated onset of intracranial hypertension due to spinal cord tumor is rare, thus, easily leading to misdiagnosis and delay in effective treatment.

Case presentation

Herein, we describe a 45-year-old female patient who manifested isolated symptoms and signs of intracranial hypertension and whose condition was initially diagnosed as idiopathic intracranial hypertension and transverse sinus stenosis. The patient received a stent implantation; however, no improvements were observed. One year later her symptoms exacerbated, and during rehospitalization a spinal imaging examination revealed a lumbar tumor. Pathologic evaluation confirmed schwannoma, and tumor resection significantly improved her symptoms, except for poor vision.

Conclusions

Space-occupying lesions of the spine should be considered in the differential diagnosis of idiopathic intracranial hypertension, even in the absence of spine-localized signs or symptoms.
The effect of anti-cancer and anti-tuberculosis treatments in lung cancer patients with active tuberculosis: a retrospective analysis
Authors: Chai Mei , Shi Qingming
Published: November 2020

Background

Lung tuberculosis (TB) and lung cancer have a complex relationship. Data concerning TB treatment in lung cancer patients are still incomplete. The aim of this study was to investigate the effects of anti-cancer and anti-tuberculosis treatments in lung cancer patients with active lung TB.

Methods

In a retrospective cohort study, lung cancer patients with active lung TB were identified between January 2013 and December 2016. Age- and sex-matched lung cancer patients without tuberculosis were selected as control subjects. Anti-cancer and anti-tuberculosis treatments were administered according to the national guidelines. The clinical courses and responses of lung cancer patients with and without active lung TB were examined and compared.

Results

A total of 31 consecutive lung cancer patients were diagnosed with active lung TB. Fifty-one lung cancer patients without TB were enrolled as control subjects. Most patients in the two groups were elderly, had advanced non-small cell lung cancer and had tumor burdens. The anti-cancer treatment completion rate and response rate were not different between two group (87.1% in TB treatment patients vs. 92.2% in lung cancer patients, 77.4% in TB treatment patients vs. 88.2% in lung cancer patients, respectively). The anti-tuberculosis treatment completion rate and success rate was 87.1 and 80.7%. The median survival times were not different between two groups (52 weeks in TB treatment patients vs. 57 weeks in lung cancer patients). The change in Karnofsky performance score was also not different between two groups. The most common side effect in TB treatment patients was liver injury (61.3%). The most serious side effect in TB treatment patients was leukocyte deficiency (9.7% in Grade 3). Both of side effects mentioned above were not different between two groups.

Conclusion

Both anti-cancer and anti-tuberculosis treatments can be safely and effectively administered in lung cancer patients with active lung TB. Attention should be paid to the risk of tuberculosis in lung cancer patients in TB high-burden countries.
Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes
Authors: Maier Anna-Karina B. , Arani Parisa , Pahlitzsch Milena , Davids Anja-Maria , Pilger Daniel , Klamann Matthias K. J. , Winterhalter Sibylle
Published: November 2020

Background

To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG).

Methods

In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups.

Results

Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p >  0.05). The number of antiglaucoma medications did not change in both groups (p >  0.05) and showed no significant difference between the two groups (p >  0.05).

Conclusion

Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation.
A case of dense pigment deposition of the posterior lens capsule
Authors: Trampuž Igor Šivec
Published: November 2020

Background

Pigment dispersion syndrome (PDS) is a well-known entity which can lead to pigmentary glaucoma (PG). This case report presents a rare presentation of PG with bilateral dense pigment deposits of the posterior lens capsule.

Case presentation

A 72-year-old male came for his first appointment due to an asymmetric worsening of visual acuity. The examination showed unilaterally severely increased intraocular pressure, bilateral dense pigment deposition of the posterior lens capsule, and a shallow unilateral optic disk excavation. Gonioscopy revealed moderate pigmentation of the angle and a concave configuration of the peripheral iris in both eyes. The standard slit lamp examination showed no transillumination defects of either iris. Optical coherence tomography showed retinal nerve fiber layer (RNFL) thinning in the peripapillary and macular regions. An antiglaucoma medication was prescribed with a good lowering effect.

Conclusion

Pigment deposition of the posterior lens capsule, which has been rarely reported, is a possible important sign of PDS or PG.
Effect of biomechanical properties on myopia: a study of new corneal biomechanical parameters
Authors: Han Fang , Li Mengdi , Wei Pinghui , Ma Jiaonan , Jhanji Vishal , Wang Yan
Published: November 2020

Background

To assess the corneal stress-strain index (SSI), which is a marker for material stiffness and corneal biomechanical parameters, in myopic eyes.

Methods

A total of 1054 myopic patients were included in this study. Corneal visualisation Scheimpflug technology was used to measure the SSI. Corneal biomechanics were assessed using the first and second applanation times (A1-and A2-times); maximum deflection amplitude (DefAmax); deflection area (HCDefArea); the highest concavity peak distance (HC-PD), time (HC-time), and deflection amplitude (HC-DefA); integrated radius (IR); whole eye movement (WEM); stiffness parameter (SP-A1;, biomechanically corrected intraocular pressure (BIOP); and Corvis biomechanical index (CBI). Scheimpflug tomography was used to obtain the mean keratometery (Km) and central corneal thickness (CCT). According to the spherical equivalent (SE) (low myopia: SE ≥ − 3.00D and high myopia: SE ≤ − 6.00D.), the suitable patients were divided into two groups.

Results

The mean SSI value was 0.854 ± 0.004. The SSI had a positive correlation with A1-time ((r = 0.272), HC-time (r = 0.218), WEM (r = 0.288), SP-A1 (r = 0.316), CBI (r = 0.199), CCT (r = 0.125), bIOP (r = 0.230), and SE (r = 0.313) (all p-values<0.01). The SSI had a negative correlation with HCDefA (r = − 0.721), HCDefArea (r = − 0.665), HC-PD(r = − 0.597), IR (r = − 0.555), DefAmax (r = − 0.564), and Km (r = − 0.103) (all p-values<0.01). There were significant differences in SSI (t = 8.960, p<0.01) and IR (t = − 3.509, p<0.01) between the low and high myopia groups.

Conclusions

In different grades of myopia, the SSI values were lower in eyes with higher SEs. It indicates that the mechanical strength of the cornea may be compromised in high myopia. The SSI was positively correlated with the spherical equivalent, and it may provide a new way to study the mechanism of myopia.
Predictors of child resilience in a community-based cohort facing flood as natural disaster
Authors: Arshad Muhammad , Mughal Muhammad Kashif , Giallo Rebecca , Kingston Dawn
Published: November 2020

Background

Natural disasters are unpredictable and uncontrollable events that usually induce significant level of stress and social disruption in afflicted individuals. The consequences are formidable, affecting lifetime health and economic prosperity. Among natural disasters, floods are the most common causes and tend to have the highest economic burden. The aim of this study was to examine factors associated with child resilience in the face of the natural disaster experienced by the city of Calgary, Alberta, Canada during its unprecedented flood of 2013.

Methods

The current study was conducted in a community-based cohort situated in the city of Calgary. The participants were recruited out of the All Our Families longitudinal cohort within the Cummings School of Medicine at the University of Calgary. Of the total 1711 people contacted, 469 people consented and completed questionnaire. Of those 469 who consented to be part of the study, 467 were eligible to be included for analysis. A flood impact questionnaire was delivered 6 months after the 2013 flood in families whose children were an average of 3 years old. Mother reported questionnaires were used to assess child resilience. The study included maternal data on a range of factors including socio-demographic, history of mental health, relationship with the partner and social support. Child related data were also incorporated into the study, and variables included delivery mode, child sex, and child age at the time of disaster.

Results

Child resilience was best predicted by mother’s age and social support, and by child gender, the child’s externalizing and internalizing behaviors and the Rothbart temperament scale: effortful control. Furthermore, this study revealed that children who were more exposed to the flood events, showed higher resilience compared to the children who were less or not exposed.

Conclusions

These findings highlight the risk and protective factors that predict child resilience and suggest that mother reported questionnaire are useful tools to assess child resilience amidst early life adversity.
Association of dietary fatty acids and the incidence risk of cardiovascular disease in adults: the Tehran Lipid and Glucose Prospective Study
Authors: Mirmiran Parvin , Houshialsadat Zeinab , Bahadoran Zahra , Khalili-Moghadam Sajad , Sheikholeslami Farhad , Azizi Fereidoun
Published: November 2020

Background

Considering the inconsistent available findings regarding the cardioprotective effect of dietary fatty acid composition, we prospectively examined the feasible association between the dietary fatty acids and the cardiovascular disease (CVD) incidence in framework of the population-based Tehran Lipid and Glucose Study.

Methods

A total of 2369 participants (19–70 years, 43.5% men) without CVD at baseline (2006–2008) were included and followed-up for 6.7 years. Fatty acids’ dietary intake was estimated using a 168-item semi-quantitative food frequency questionnaire. The CVD incidence risk across tertiles of dietary fatty acids was predicted via Cox proportional hazards regression models.

Results

The average age and body mass index of the included population were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Over 6.7 years of follow-up, 79 cases of CVD were detected. The risk of CVD was lower in upper tertile of monounsaturated fatty acids, oleic acid, and docosahexaenoic acid + eicosapentaenoic acid among the tertiles. No significant associations were found between total fat, saturated and polyunsaturated fatty acids’ intake, and CVD.

Conclusions

Our results suggest that the dietary fatty acid composition might affect the incidence risk of CVD within the Iranian population.
COVID-19 mortality risk for older men and women
Authors: Yanez N. David , Weiss Noel S. , Romand Jacques-André , Treggiari Miriam M.
Published: November 2020

Background

Case-fatality from COVID-19 has been reported to be relatively high in patients age 65 years or older. We sought to determine the age-specific rates of COVID-19 mortality at the population level.

Methods

We obtained information regarding the total number of COVID-19 reported deaths for six consecutive weeks beginning at the 50th recorded death, among 16 countries that reported a relatively high number of COVID-19 cases as of April 12, 2020. We performed an ecological study to model COVID-19 mortality rates per week by age group (54 years or younger, 55–64 years, and 65 years or older) and sex using a Poisson mixed effects regression model.

Results

Over the six-week period of data, there were 178,568 COVID-19 deaths from a total population of approximately 2.4 billion people. Age and sex were associated with COVID-19 mortality. Compared with individuals ages 54 years or younger, the incident rate ratio (IRR) was 8.1, indicating that the mortality rate of COVID-19 was 8.1 times higher (95%CI = 7.7, 8.5) among those 55 to 64 years, and more than 62 times higher (IRR = 62.1; 95%CI = 59.7, 64.7) among those ages 65 or older. Mortality rates from COVID-19 were 77% higher in men than in women (IRR = 1.77, 95%CI = 1.74, 1.79).

Conclusions

In the 16 countries examined, persons age 65 years or older had strikingly higher COVID-19 mortality rates compared to younger individuals, and men had a higher risk of COVID-19 death than women.
Gender differences in managers’ attitudes towards employees with depression: a cross-sectional study in Sweden
Authors: Mangerini Ilaria , Bertilsson Monica , de Rijk Angelique , Hensing Gunnel
Published: November 2020

Background

Depression is prevalent among employees and a major reason for sickness absence. First-line managers’ attitudes towards employees with depression might influence return to work and the scant literature indicates gender differences in attitudes. The objective of this study was to investigate gender differences in managers’ attitudes to employees with depression.

Methods

A cross-sectional study was conducted among 4737 Swedish managers in 2017 (response rate 71%, n = 3358). Attitudes towards depression were measured with the instrument “Managerial stigma towards employees with depression” (12 items). The response patterns of women and men, the level of stigma and the direction of the gender differences were investigated with independent t tests and binary logistic regression analyses with covariates.

Results

The likelihood of reporting high negative attitudes (score ≥ 36) was lower among women than men (odds ratio, 1.64; 95% confidence interval, 1.28–2.10) after adjusting for age, level of education, work sector, distribution of women and men among the staff, current workplace experience in management, lifetime experience in management, managerial position and presence of staff members at the current workplace who had depression and/or anxiety disorders.

Conclusions

Based on these findings, a gender-sensitive approach is suggested for future interventions to improve managers’ attitudes towards employees with depression and other mental disorders.
Polymorphisms in the airway epithelium related genes CDHR3 and EMSY are associated with asthma susceptibility
Authors: Zhang Miaomiao , Chen Guo , Wang Yu , Wu Shou-Quan , Sandford Andrew J. , He Jian-Qing
Published: November 2020

Background

As a main line of defense of the respiratory tract, the airway epithelium plays an important role in the pathogenesis of asthma.CDHR3andEMSYwere reported to be expressed in the human airway epithelium. Although previous genome-wide association studies found that the two genes were associated with asthma susceptibility, similar observations have not been made in the Chinese Han population.

Methods

A total of 300 asthma patients and 418 healthy controls unrelated Chinese Han individuals were enrolled. Tag-single nucleotide polymorphisms (Tag-SNPs) were genotyped and the associations between SNPs and asthma risk were analyzed by binary logistic regression analysis.

Results

After adjusting for confounding factors, the A allele of rs3847076 inCDHR3was associated with increased susceptibility to asthma (OR = 1.407, 95% CI: 1.030–1.923). For theEMSYgene, the T alleles of both rs2508746 and rs12278256 were related with decreased susceptibility to asthma (additive model: OR = 0.718, 95% CI: 0.536–0.961; OR = 0.558, 95% CI: 0.332–0.937, respectively). In addition, the GG genotype of rs1892953 showed an association with increased asthma risk under the recessive model (OR = 1.667, 95% CI: 1.104–2.518) and the GATCTGAGT haplotype inEMSYwas associated with reduced asthma risk (P = 0.037).

Conclusions

This study identified novel associations of rs3847076 inCDHR3, as well as rs1892953, rs2508746 and rs12278256 inEMSYwith adult asthma susceptibility in the Chinese Han population. Our observations suggest thatCDHR3andEMSYmay play important roles in the pathogenesis of asthma in Chinese individuals. Further study with larger sample size is needed.
Sternal cavernous hemangioma and reconstruction of the anterior chest wall: a case report
Authors: Fernández-Trujillo Liliana , Sangiovanni Saveria , Morales Eliana I. , Marin Valeria , Sua Luz F. , Velasquez Mauricio
Published: November 2020

Background

The sternum is considered an unusual tumor site, corresponding to 15% of all thoracic wall tumors. Primary sternal tumors are even rarer and most commonly malignant. We present the case of a young man who consulted with a painful sternal mass, which after its resection is confirmed to be a cavernous hemangioma.

Case presentation

A 39-year-old man, with unremarkable medical history besides a 2-year-long sternal pain, non-irradiated, which worsens over the last few months and is accompanied by the appearance of a sternal palpable mass. On physical exam, there was a bulging of the sternal manubrium, with no inflammatory changes. Thoracic CT scan shows an expansive and lytic lesion of the sternum, compromising the manubrium and extending to the third sternocostal joint, without intrathoracic compromise nor cleavage plane with mediastinal vascular structures. The patient is taken to resection of the mass and sternal reconstruction using prosthetic material and pectoral and fasciocutaneous muscular flaps. Histopathological findings: cavernous hemangioma with negative borders and no other malignant findings.

Conclusions

Sternal hemangiomas can cause defects in the bone structure and show an expansive growth, challenging the differentiation between a benign or malignant lesion. Therefore, they should be considered malignant until shown otherwise. Management involves radical surgery with curative purposes and posterior reconstruction to improve quality of life, as shown with our patient.
Larval habitats and species diversity of mosquitoes (Diptera: Culicidae) in West Azerbaijan Province, Northwestern Iran
Authors: Amini Mojtaba , Hanafi-Bojd Ahmad Ali , Aghapour Ali Ahmad , Chavshin Ali Reza
Published: November 2020

Background

The characteristics of a larval habitat is an important factor which affects the breeding pattern and population growth of mosquitoes Information about the larval habitat characteristics and pupal productivity can be utilized for the surveillance of the level of population growth, species diversity, and preferred breeding sites of mosquitoes, which are important aspects of integrated vector control. In the present study, mosquito larvae were collected from 22 natural habitats in five counties of the West Azerbaijan Province in the Northwest of Iran during May–November 2018. Physicochemical characteristics of the habitats were investigated. These included alkalinity, chloride (Cl) content, water temperature (°C), turbidity (NTU), Total Dissolved Solids (TDS) (ppm), Electrical Conductivity (EC) (μS/cm), and acidity (pH). The index of affinity between the collected species was calculated using Fager & McGowan test.

Results

A total of 2715 specimens were collected and identified. Seven different species belonging to four genera were identified in our study sites. The species included, Culex pipiensLinnaeus 1758,Culex theileriTheobald 1903, Culex mimeticusNoé 1899,Culex modestusFicalbi 1947, Culiseta longiareolataMacquart 1838, Anopheles maculipennisMeigen 1818complex, andAedes caspiusPallas 1771. There was a significant difference in chloride content and water temperature preferences among the different species (P < 0.05). Also, there was no significant difference in pH, Alkalinity, Turbidity, TDS, and EC preferences among the different species (P > 0.05). The affinity between the pair of species Cx. mimeticus/Cs. longiareolata was 0.526. There was no affinity between other pairs of species or the affinity was very weak.

Conclusions

The physicochemical and biological characteristics of mosquito larval habitats play an important role in zoning of areas suitable for breeding and distribution. Surveillance of these characteristics can provide valuable information for entomological monitoring of mosquito vectors and for designing targeted control programs. Also, further studies should be undertaken in a wider geographical area, taking into account the complex characteristics of the physicochemical and ecological factors of the study area and their interaction with various mosquito species.
Does prophylactic antibiotic administration for tooth extraction affect PT-INR in patients taking warfarin?
Authors: Iwata Eiji , Tachibana Akira , Kusumoto Junya , Takata Naoki , Hasegawa Takumi , Akashi Masaya
Published: November 2020

Background

Various antibiotics and analgesics have been reported to interact with warfarin. Reports that investigate the effects of medication taken for just a few days during tooth extraction on the prothrombin time-international normalized ratio are rare.

Methods

A total of 110 patients receiving long-term stable warfarin therapy underwent tooth extraction without interruption of warfarin treatment. INR values were measured 1 month before the tooth extraction, the day of the extraction, and 1 week after the extraction. We investigated the changes in INR values between the day of extraction and 1 week after extraction, as well as the various risk factors for increases in INR values.

Results

Before and after tooth extraction, the number of patients taking cefcapene pivoxil, amoxicillin, and azithromycin was 57, 36, and 8, respectively. Nine patients were administered ampicillin before tooth extraction and received amoxicillin after their tooth extraction. One week after tooth extraction, the INR values increased beyond the therapeutic range in 3 out of 110 patients (2.7%). The INR values before tooth extraction in these three patients were close to 3.0. The INR value increased by more than twice as much in 1 out of 110 patients (0.9%).

Conclusion

Our results suggest that prophylactic antibiotic administration has little effect on INR values when patients on stable warfarin therapy undergo tooth extraction. Surgeons have to take attention if the patients whose INR values are close to 3.0 before their extraction.
Network pharmacology exploration reveals a common mechanism in the treatment of cardio-cerebrovascular disease with Salvia miltiorrhiza Burge. and Carthamus tinctorius L
Authors: Wang Yu , Shi Yajun , Zou Junbo , Zhang Xiaofei , Liang Yulin , Tai Jia , Cui Chunli , Wang Mei , Guo Dongyan
Published: November 2020

Background

This study aimed to identify the key genes and KEGG pathways inCarthamus tinctoriusL. (Safflower) andSalvia miltiorrhizaBurge. (Salvia) for the treatment of cardio-cerebrovascular disease, and to explore their potential molecular mechanisms.

Methods

Compounds and targets in Safflower and Salvia were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We obtained targets of myocardial infarction (MI) and cerebral infarction (CI) data from Therapeutic Target Database (TTD), Drugbank and DisGeNET datasets. The network of Safflower, Salvia, CI and MI was established and then executing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the functional characteristics were performed. The Chinese herbal prescription and target for CI and MI were obtained by searching in the database. Finally, the main pathways of Salvia and Safflower in Chinese patent medicines were analyzed. The MCAO model was established in rats, and compatibility of salvia with safflower was experimentally verified.

Results

We obtained a total of 247 genes targeted by 52 compounds from Safflower and 119 genes targeted by 48 compounds from Salvia. In total, we identified 299 known therapeutic targets for the treatment of CI and 960 targets for the treatment MI. There are 23 common targets for Salvia, Safflower, MI, and CI. A total of 85 KEGG pathways were also enriched and intersected with the pathway of proprietary Chinese medicine to yield 25 main pathways. Safflower and Salvia have the best therapeutic effect in MCAO.

Conclusion

We identified gene lists for Safflower and Salvia in CI and MI. Bioinformatics and interaction analyses may provide new insight into the treatment of cardio-cerebrovascular diseases with Safflower and Salvia.
Sharing genomic data from clinical testing with researchers: public survey of expectations of clinical genomic data management in Queensland, Australia
Authors: Vidgen Miranda E. , Kaladharan Sid , Malacova Eva , Hurst Cameron , Waddell Nicola
Published: November 2020

Background

There has been considerable investment and strategic planning to introduce genomic testing into Australia’s public health system. As more patients’ genomic data is being held by the public health system, there will be increased requests from researchers to access this data. It is important that public policy reflects public expectations for how genomic data that is generated from clinical tests is used. To inform public policy and discussions around genomic data sharing, we sought public opinions on using genomic data contained in medical records for research purposes in the Australian state of Queensland.

Methods

A total of 1494 participants completed an online questionnaire between February and May 2019. Participants were adults living in Australia. The questionnaire explored participant preferences for sharing genomic data or biological samples with researchers, and concerns about genomic data sharing.

Results

Most participants wanted to be given the choice to have their genomic data from medical records used in research. Their expectations on whether and how often they needed to be approached for permission on using their genomic data, depended on whether the data was identifiable or anonymous. Their willingness to sharing data for research purposes depended on the type of information being shared, what type of research would be undertaken and who would be doing the research. Participants were most concerned with genomics data sharing that could lead to discrimination (insurance and employment), data being used for marketing, data security, or commercial use.

Conclusions

Most participants were willing to share their genomic data from medical records with researchers, as long as permission for use was sought. However, the existing policies related to this process in Queensland do not reflect participant expectations for how this is achieved, particularly with anonymous genomics data. This inconsistency may be addressed by process changes, such as inclusion of research in addition to clinical consent or general research data consent programs.
Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study
Authors: Auger Nathalie , Paradis Gilles , Low Nancy , Ayoub Aimina , He Siyi , Potter Brian J.
Published: November 2020

Background

Cannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women.

Methods

We analyzed a longitudinal cohort of 1,247,035 pregnant women in Quebec, Canada, between 1989 and 2019. The main exposure was current or past history of cannabis use disorders at cohort entry. The main outcome measure included future hospital admission for any cardiovascular disorder during 18,998,986 person years of follow-up. We used Cox proportional hazards regression models adjusted for patient characteristics to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of cannabis use disorder with the later risk of cardiovascular hospitalization.

Results

Women with cannabis use disorders had a higher incidence of cardiovascular hospitalization than unexposed women (58.4 vs. 33.6 per 10,000 person years). Cannabis use disorder was associated with 1.48 times the risk of cardiovascular hospitalization (95% CI 1.27–1.72), compared with no cannabis use disorder. The association was greater for cannabis with concomitant use of other substances (HR 1.84, 95% CI 1.53–2.21) than for cannabis alone (HR 1.30, 95% CI 0.99–1.72). Cannabis use disorder was strongly associated with hemorrhagic stroke, even with adjustment for other substance use (HR 2.08, CI 1.07–4.05).

Conclusions

Cannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.
Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs
Authors: Burnett Thomas , Mozgunov Pavel , Pallmann Philip , Villar Sofia S. , Wheeler Graham M. , Jaki Thomas
Published: November 2020

Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. Despite much research in the statistical literature highlighting the potential advantages of adaptive designs over traditional fixed designs, the uptake of such methods in clinical research has been slow. One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.
Molecular characterization of isolated infectious bronchitis viruses from affected vaccinated broiler flocks in Syria
Authors: Al-Jallad Tamara , Kassouha Morshed , Salhab Mohamad , Alomar Anouar , AL-Masalma Mouhamad , Abdelaziz Fahim
Published: November 2020

Background

Avian Infectious Bronchitis Virus (IBV) is a highly contagious disease that imposes a huge economic burden on the global poultry industry. IBV contains numerous serotypes and variants with incomplete tenuous cross immunological protection. The failure of currently used vaccines to protect against diverse, circulating IBV strains that are specific to a given region poses a major problem for the poultry industry. Thus, there is an urgent need to conduct studies aimed at genotyping field IB viruses. In this study, we have determined the molecular characteristics of circulating IBV by sequencing the S1 gene of viral isolates from affected previously vaccinated broiler flocks suffering from the disease.

Results

Ten isolates propagated in embryonated eggs showed an ability to induce typical IBV lesions after three successive viral passages. We performed a nested RT–PCR assay that targeted the hypervariable region 3 (HVR-3) of the S1 gene, and identified the isolates as IBV through sequence analysis. The IBV isolates showed sequence similarity between the Syrian isolates that vary from 96.20 to 100%, and those being closer to the Variant-2 strain IS/1494/06 (EU780077.2) with 97.5 to 99.4% similarities. However, less nucleotide identity was found with sequences belonging to the used vaccine strains such as H120, Mass5, and 4/91.

Conclusions

This study showed the presence of the Variant-2 strain circulating in Syrian broiler flocks showing signs of IBV disease. Currently, there is no commercial effective vaccine which protects birds against the Variant-2 strain. Continuous monitoring procedures should be taken to control and limit the spread of the IBV Variant-2 strain. This research emphasizes both the importance of epidemiological monitoring in intensive poultry farming for novel pathogens and the use of local isolates as future vaccine targets.
Treatment-related biomarkers in pulmonary hypertension patients on oral therapies
Authors: Swaminathan Aparna C. , Zhu Hongmei , Tapson Victor , Lokhnygina Yuliya , Poms Abby , Kelleher Zach , Gaspard Elijah , Kennedy Karla , Fee Brian E. , Fortin Terry , Mason S. Nicholas , Parikh Kishan , McMahon Tim J.
Published: November 2020

Background

Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.

Methods

This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis.

Results

The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (25.9%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p = 0.03 respectively), and ET-1 predicted future 6MWD (p = 0.02). ET-1 (p = 0.01) and cGMP/NT-proBNP ratio (p = 0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p = 0.03) and PAH patients on ERA therapy (p = 0.01).

Conclusions

ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.
CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR-584-5p
Authors: Zhang Yanhe , Wang Hui , Li Chao , Gao Linlin , Zheng Yayun , Chang Wenjuan , Lu Chao , Zhao Xiaoguang
Published: November 2020

Background

There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism.

Methods

The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay andSpearmancorrelation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells.

Results

CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC.

Conclusion

CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.
The quality of dietary carbohydrate and fat is associated with better metabolic control in persons with type 1 and type 2 diabetes
Authors: Jacobsen Sabine S. , Vistisen Dorte , Vilsbøll Tina , Bruun Jens M. , Ewers Bettina
Published: November 2020

Background

Diet quality is generally poor in persons with diabetes and it is unknown whether this is associated with worse glycaemic control and atherogenic lipid profile. The aim was to examine diet quality in relation to important markers of metabolic control in adults with type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods

The study was cross-sectional and included 423 (49% females) persons with T1D and 339 (29% females) persons with T2D recruited from an outpatient diabetes clinic in Denmark. Data were collected from July 2014 to January 2015. Diet quality was assessed with a food frequency questionnaire to examine eight key dietary components (carbohydrates, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, added sugar, dietary fibre, fruit and vegetables). Clinical data assessing metabolic control (haemoglobin A1c (HbA1c), total cholesterol (total C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure and body mass index were extracted from the electronic medical records.

Results

In T1D, higher intake of carbohydrates and added sugar was associated with higher HbA1c; higher fruit intake was associated with lower total C and LDL-C; and higher intake of carbohydrates and dietary fibre was associated with lower HDL-C. In T2D, higher intake of saturated fat was associated with higher total C; higher intake of added sugar was associated with higher LDL-C; and higher intake of polyunsaturated fat was associated with higher diastolic blood pressure.

Conclusions

In Danish adults with T1D and T2D, both the total intake and the quality of carbohydrates and fat were associated with an unfavourable glucose regulation and lipid profile. Thus, our findings support a constant focus on diet and emphasise the need for dietary support in people with diabetes to improve diet quality, metabolic control and possibly reduce cardiovascular risk.
Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy
Authors: Sheta Razan , Bachvarova Magdalena , Plante Marie , Renaud Marie-Claude , Sebastianelli Alexandra , Gregoire Jean , Navarro Jamilet Miranda , Perez Ricardo Bringas , Masson Jean-Yves , Bachvarov Dimcho
Published: November 2020

Background

Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as “BRCAness”. Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified.

Methods

We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids.

Results

The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%–60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples.

Conclusion

The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial.