bluuebunny/crossref_metadata_2025 huggingface dataset:
Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion
Authors: Kim Michael D. , Baumlin Nathalie , Dennis John S. , Yoshida Makoto , Kis Adrian , Aguiar Carolina , Schmid Andreas , Mendes Eliana , Salathe Matthias
Published: September 2020

The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in anin vitromodel and a small clinical trial.

Primary human bronchial epithelial cells (HBECs) were differentiated at the air–liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression ofMUC5AC,TGF-β1, andMMP-9mRNAs was measured before and after losartan treatment.

In vitro, CS exposure of HBECs caused a significant increase in mRNA expression ofMUC5ACandTGF-β1and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease inMUC5ACexpression and mucus concentrations, partially by inhibiting TGF-β signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels ofMUC5AC,TGF-β1, andMMP-9in the upper airways after 2 months of losartan treatment.

Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases.
Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study
Authors: Al-Hashel Jasem Y. , Ismail Ismail Ibrahim
Published: September 2020

Background

Since the declaration COVID-19 as a pandemic, healthcare systems around the world have faced a huge challenge in managing patients with chronic diseases. Patients with migraine were specifically vulnerable to inadequate medical care. We aimed to investigate the “real-world” impact of COVID-19 pandemic on migraine patients, and to identify risk factors for poor outcome.

Methods

We administered an online, self-reported survey that included demographic, migraine-related, COVID-19-specific and overall psychosocial variables between July 15 and July 30, 2020. We recruited a sample of patients with migraine from headache clinic registry and via social media to complete an anonymous survey. Outcomes included demographic variables, change in migraine frequency and severity during the lockdown period, communication with treating physician, compliance to migraine treatment, difficulty in getting medications, medication overuse, symptoms of anxiety and/or depression, sleep and eating habits disturbance, screen time exposure, work during pandemic, use of traditional medicine, effect of Botox injection cancellation, and overall worries and concerns during pandemic.

Results

A total of 1018 patients completed the survey. Of the respondents, 859 (84.3%) were females; 733 (71.9%) were aged 20 to 40 years, 630 (61.8%) were married, and 466 (45.7%) reported working during the pandemic.

In comparison to pre-pandemic period, 607 respondents (59.6%) reported increase in migraine frequency, 163 (16%) reported decrease in frequency, and 105 (10.3%) transformed to chronic migraine. Severity was reported to increase by 653 (64.1%) respondents. The majority of respondents; 626 (61.5%) did not communicate with their neurologists, 477 (46.9%) reported compliance to treatment, and 597 (58.7%) reported overuse of analgesics. Botox injections cancellation had a negative impact on 150 respondents (66.1%) from those receiving it. Forty-one respondents (4%) were infected with COVID-19; 26 (63.4%) reported worsening of their headaches amid infection period. Sleep disturbance was reported by 794 (78.1%) of respondents, and 809 (79.5%) reported having symptoms of anxiety and/or depression.

Conclusions and relevance

COVID-19 pandemic had an overall negative impact on patients with migraine. Several risk factors for poor outcome were identified. Long-term strategies should be validated and implemented to deliver quality care for patients with migraine, with emphasis on psychosocial well-being.
Floral signals evolve in a predictable way under artificial and pollinator selection in Brassica rapa
Authors: Zu Pengjuan , Schiestl Florian P. , Gervasi Daniel , Li Xin , Runcie Daniel , Guillaume Frédéric
Published: September 2020

Background

Angiosperms employ an astonishing variety of visual and olfactory floral signals that are generally thought to evolve under natural selection. Those morphological and chemical traits can form highly correlated sets of traits. It is not always clear which of these are used by pollinators as primary targets of selection and which would be indirectly selected by being linked to those primary targets. Quantitative genetics tools for predicting multiple traits response to selection have been developed since long and have advanced our understanding of evolution of genetically correlated traits in various biological systems. We use these tools to predict the evolutionary trajectories of floral traits and understand the selection pressures acting on them.

Results

We used data from an artificial selection and a pollinator (bumblebee, hoverfly) evolution experiment with fast cyclingBrassica rapaplants to predict evolutionary changes of 12 floral volatiles and 4 morphological floral traits in response to selection. Using the observed selection gradients and the genetic variance-covariance matrix (G-matrix) of the traits, we showed that the observed responses of most floral traits including volatiles were predicted in the right direction in both artificial- and bumblebee-selection experiment. Genetic covariance had a mix of constraining and facilitating effects on evolutionary responses. We further revealed that G-matrices also evolved in the selection processes.

Conclusions

Overall, our integrative study shows that floral signals, especially volatiles, evolve under selection in a mostly predictable way, at least during short term evolution. Evolutionary constraints stemming from genetic covariance affected traits evolutionary trajectories and thus it is important to include genetic covariance for predicting the evolutionary changes of a comprehensive suite of traits. Other processes such as resource limitation and selfing also need to be considered for a better understanding of floral trait evolution.
Siberian larch (Larix sibirica Ledeb.) mitochondrial genome assembled using both short and long nucleotide sequence reads is currently the largest known mitogenome
Authors: Putintseva Yuliya A. , Bondar Eugeniya I. , Simonov Evgeniy P. , Sharov Vadim V. , Oreshkova Natalya V. , Kuzmin Dmitry A. , Konstantinov Yuri M. , Shmakov Vladimir N. , Belkov Vadim I. , Sadovsky Michael G. , Keech Olivier , Krutovsky Konstantin V.
Published: September 2020

Background

Plant mitochondrial genomes (mitogenomes) can be structurally complex while their size can vary from ~ 222 Kbp in Brassica napus to 11.3 Mbp in Silene conica. To date, in comparison with the number of plant species, only a few plant mitogenomes have been sequenced and released, particularly for conifers (the Pinaceae family). Conifers cover an ancient group of land plants that includes about 600 species, and which are of great ecological and economical value. Among them, Siberian larch (Larix sibirica Ledeb.) represents one of the keystone species in Siberian boreal forests. Yet, despite its importance for evolutionary and population studies, the mitogenome of Siberian larch has not yet been assembled and studied.

Results

Two sources of DNA sequences were used to search for mitochondrial DNA (mtDNA) sequences: mtDNA enriched samples and nucleotide reads generated in the de novo whole genome sequencing project, respectively. The assembly of the Siberian larch mitogenome contained nine contigs, with the shortest and the largest contigs being 24,767 bp and 4,008,762 bp, respectively. The total size of the genome was estimated at 11.7 Mbp. In total, 40 protein-coding, 34 tRNA, and 3 rRNA genes and numerous repetitive elements (REs) were annotated in this mitogenome. In total, 864 C-to-U RNA editing sites were found for 38 out of 40 protein-coding genes. The immense size of this genome, currently the largest reported, can be partly explained by variable numbers of mobile genetic elements, and introns, but unlikely by plasmid-related sequences. We found few plasmid-like insertions representing only 0.11% of the entire Siberian larch mitogenome.

Conclusions

Our study showed that the size of the Siberian larch mitogenome is much larger than in other so far studied Gymnosperms, and in the same range as for the annual flowering plant Silene conica (11.3 Mbp). Similar to other species, the Siberian larch mitogenome contains relatively few genes, and despite its huge size, the repeated and low complexity regions cover only 14.46% of the mitogenome sequence.
Coronary artery segmentation in angiographic videos utilizing spatial-temporal information
Authors: Wang Lu , Liang Dongxue , Yin Xiaolei , Qiu Jing , Yang Zhiyun , Xing Junhui , Dong Jianzeng , Ma Zhaoyuan
Published: September 2020

Background

Coronary artery angiography is an indispensable assistive technique for cardiac interventional surgery. Segmentation and extraction of blood vessels from coronary angiographic images or videos are very essential prerequisites for physicians to locate, assess and diagnose the plaques and stenosis in blood vessels.

Methods

This article proposes a novel coronary artery segmentation framework that combines a three–dimensional (3D) convolutional input layer and a two–dimensional (2D) convolutional network. Instead of a single input image in the previous medical image segmentation applications, our framework accepts a sequence of coronary angiographic images as input, and outputs the clearest mask of segmentation result. The 3D input layer leverages the temporal information in the image sequence, and fuses the multiple images into more comprehensive 2D feature maps. The 2D convolutional network implements down–sampling encoders, up–sampling decoders, bottle–neck modules, and skip connections to accomplish the segmentation task.

Results

The spatial–temporal model of this article obtains good segmentation results despite the poor quality of coronary angiographic video sequences, and outperforms the state–of–the–art techniques.

Conclusions

The results justify that making full use of the spatial and temporal information in the image sequences will promote the analysis and understanding of the images in videos.
Effects of dialysis modality choice on the survival of end-stage renal disease patients in southern China: a retrospective cohort study
Authors: He Zhiren , Hou Haijing , Zhang Difei , Mo Yenan , Zhang La , Su Guobin , Lin Junjie , Lu Liming , Huang Jingyao , Gu Yewen , Zhang Ying , Lin Jingxia , Yuan Fengling , Peng Yu , Liang Hui , Zhao Daixin , Lu Fuhua , Liu Xusheng , Wang Lixin
Published: September 2020

Background

The optimal choice of treatment, with hemodialysis (HD) or peritoneal dialysis (PD), for end-stage renal disease (ESRD) patients, is still controversial. Only a few studies comparing HD and PD have been conducted in China, which has the largest number of dialysis patients in the world.

Methods

A retrospective cohort study was conducted on ESRD patients who began renal replacement treatment from January 1, 2012 to December 31, 2017 in Guangdong Provincial Hospital of Chinese Medicine. Propensity scoring match was applied to balance the baseline conditions and multivariate Cox regression analysis to compare the mortality between HD and PD patients, and evaluated the correlation between mortality and various baseline characteristics.

Results

A total of 436 HD patients and 501 PD patients were included in this study, and PD patients had better survival than HD patients, but the difference was not statistically significant. For younger ESRD patients (≤60-year-old), the overall survival of PD was better than that of HD, but HD was associated with a lower risk of death in older patients (> 70-year-old). This difference was still significant after adjustment for a variety of confounding factors. Female gender, age at dialysis initiation, cardiovascular disease, cholesterol, and HD were risk factors of all-cause mortality in the younger subgroup, while PD was risk factor in the older subgroup.

Conclusion

PD may be a better choice for younger ESRD patients, and HD for the older patients.
Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis
Authors: Li Yan , Qiu Shuang , Shi Jikang , Guo Yanbo , Li Zhijun , Cheng Yi , Liu Yawen
Published: September 2020

Background

Autism spectrum disorder (ASD) is becoming increasingly prevalent of late. Methylenetetrahydrofolate reductase (MTHFR) has a significant role in folate metabolism. Owing to the inconsistencies and inconclusiveness on the association betweenMTHFRsingle nucleotide polymorphism (SNP) and ASD susceptibilities, a meta-analysis was conducted to settle the inconsistencies.

Methods

For this meta-analysis, a total of 15 manuscripts published up to January 26, 2020, were selected from PubMed, Google Scholar, Medline, WangFang, and CNKI databases using search terms “MTHFR” OR “methylenetetrahydrofolate reductase” AND “ASD” OR “Autism Spectrum Disorders” OR “Autism” AND “polymorphism” OR “susceptibility” OR “C677T” OR “A1298C”.

Results

The findings of the meta-analysis indicated thatMTHFRC677T polymorphism is remarkably associated with ASD in the five genetic models, viz., allelic, dominant, recessive, heterozygote, and homozygote. However, theMTHFRA1298C polymorphism was not found to be significantly related to ASD in the five genetic models. Subgroup analyses revealed significant associations of ASD with theMTHFR(C677T and A1298C) polymorphism. Sensitivity analysis showed that this meta-analysis was stable and reliable. No publication bias was identified in the associations betweenMTHFRC677T polymorphisms and ASD in the five genetic models, except for the one with regard to the associations betweenMTHFRA1298C polymorphisms and ASD in the five genetic models.

Conclusion

This meta-analysis showed thatMTHFRC677T polymorphism is a susceptibility factor for ASD, andMTHFRA1298C polymorphism is not associated with ASD susceptibility.
Unilateral pulmonary vein atresia presenting with recurrent haemoptysis in a child: a case report
Authors: Wong Martin Ngie Liong , Tang Ing Ping , Chor Yek Kee , Lau Kiew Siong , John Anne Rachel , Hii King Ching , Lee Olive Pei Yi , Lim Wooi Kok , Tan Hannah Pei Koon
Published: September 2020

Background

Haemoptysis is an uncommon presenting symptom in children and is usually caused by acute lower respiratory tract infection or foreign body aspiration. We report a rare case of right unilateral pulmonary vein atresia (PVA) as the underlying aetiology of recurrent haemoptysis in a child.

Case presentation

A 4 years old girl presented with history of recurrent haemoptysis. Bronchoscopic evaluation excluded a foreign body aspiration but revealed right bronchial mucosal hyperaemia and varices. Diagnosis of right unilateral PVA was suspected on transthoracic echocardiography which demonstrated hypoplastic right pulmonary artery and non-visualization of right pulmonary veins. Final diagnosis was confirmed on cardiac CT angiography. A conservative treatment approach was opted with consideration for pneumonectomy in future when she is older.

Conclusion

Rarer causes should be considered when investigating for recurrent haemoptysis in children. Bronchoscopy and cardiac imaging are useful tools to establish the diagnosis of unilateral PVA in our case.
Mastery and self-esteem mediate the association between visual acuity and mental health: a population-based longitudinal cohort study
Authors: Maaswinkel I. M. , van der Aa H. P. A. , van Rens G. H. M. B. , Beekman A. T. F. , Twisk J. W. R. , van Nispen R. M. A.
Published: September 2020

Background

With deteriorating eyesight, people often become dependent on others for many aspects of their daily lives. As a result, they feel less ‘in control’ and experience lower self-esteem. Lower sense of mastery and self-esteem are known to predict depression, but their roles in people with visual impairment have only marginally been investigated. Therefore, this study aimed to determine the influence of mastery and self-esteem on the relationship between visual acuity and mental health.

Methods

A longitudinal cohort study was performed using data from the Longitudinal Aging Study Amsterdam (LASA), collected between 2001 and 2012. A community-based population of 2599 older adults were included, who were randomly selected from population registers. Outcomes of interest were the Pearlin Mastery Scale, Rosenberg Self-Esteem Scale, Center for Epidemiologic Studies – Depression scale and the Hospital Anxiety Depression Scale – Anxiety subscale. Linear mixed models were used to establish the association between visual acuity and mental health over time.

Results

Mean age was 72 years, 56% was female and 1.2% qualified as having low vision. Visual impairment was associated with a lower sense of mastery (β = − 0.477,p < 0.001), lower self-esteem (β = − 0.166,p = 0.008) and more depression (β = 0.235, p < 0.001). No significant association between visual acuity and anxiety was found. The relationship between visual acuity and depression was mediated by self-esteem (25%) and sense of mastery (79%).

Conclusions

Vision loss was associated with depression. This association was mediated by self-esteem and sense of mastery. This provides us with new possibilities to identify, support and treat those at risk for developing depression by aiming to increase their self-esteem and sense of mastery.
Decoding and reasoning mental states in major depression and social anxiety disorder
Authors: Maleki Gheysar , Zabihzadeh Abbas , Richman Mara J. , Demetrovics Zsolt , Mohammadnejad Fatemeh
Published: September 2020

Background

Major depression (MDD) and social anxiety (SAD) disorders are debilitating psychiatric conditions characterized by disturbed interpersonal relationships. Despite these impairments in social relationships, research has been limited in simultaneously evaluating the dysfunction in MDD or SAD within two aspects of theory of mind (ToM): decoding mental states (i.e., Affective ToM) and reasoning mental states (i.e., cognitive ToM). Taking this into consideration, the current study assesses both decoding and reasoning mental states abilities in MDD, SAD, and healthy controls (HC).

Methods

Subjects included 37 patients with MDD, 35 patients with SAD, and 35 HCs. ToM was measured with the Reading the Mind in the Eyes Test (RMET) and the Faux Pas Task, which assess decoding and reasoning mental states, respectively.

Results

Results revealed that in decoding of mental states, both the SAD and MDD groups had lower scores than the HC group; there was no significant difference between the SAD and MDD groups in decoding mental states. Conversely, in reasoning mental states, the SAD and HC groups had higher scores than the MDD group; no differences were found between the SAD and HC groups.

Conclusions

Clinicians and researchers should further consider parsing generalized impairment in ToM into two aspects: decoding and reasoning of mental states by using the aforementioned measurements. By further understanding the two aspects, we can create a potentially new clinical profile for mental health disorders, such as in this context with both decoding and reasoning mental state impairment in MDD and just a decoding impairment in SAD.
The effect of the presence of children on adult smoking behaviour: empirical evidence based on China family panel studies
Authors: Lin Haoxiang , Chang Chun , Liu Zhao , Tan Huaqing
Published: September 2020

Background

Despite a number of studies linking family and marriage factors with health behaviour, the effects of children on the health behaviour of parents are still understudied. This study explored the association between the presence of children and adults’ smoking behaviours.

Methods

This study used panel data from the China Family Panel Studies 2010 and 2012, and the data set included 23,157 households and 45,513 adults. Logistic regression was performed to analyse the association of the presence of children on adults’ smoking behaviours. Subgroup regression was used to examine heterogeneous effects.

Results

Full sample regressions showed that the number of children was significantly inversely associated with smoking behaviour (OR = 0.93; 95% 0.90–0.96). Further subsample regression finds that such effect is only significant among the high-education group (OR = 0.92; 95% 0.87–0.97), high-skill workers (OR = 0.89; 95% 0.80–0.99) and couples who had an age gap greater than 2 years (OR = 0.91; 95% 0.88–0.95).

Conclusions

Our findings confirm the existence of the upward intergenerational effect of the presence of children on adults’ smoking behaviour in China. However, such effects are not equal across all demographic characteristics. Future research could explore other parts of the upward mechanism and possible pathways for a stronger effect. In resource-poor areas, targeting cessation activities at those who have children at an early age may be an effective strategy.
Biomechanical comparison between single-row with triple-loaded suture anchor and suture-bridge double-row rotator cuff repair
Authors: He He-Bei , Hu Yong , Li Chuan , Li Cheng-Guo , Wang Min-Cong , Zhu Hui-Feng , Yan Zhi-Wen , Pan Cheng-Long , Wang Tao
Published: September 2020

Background

Numerous biomechanical and clinical studies comparing different techniques for rotator cuff repair have been reported, yet universal consensus regarding the superior technique has not achieved. A medially-based single-row with triple-loaded suture anchor (also referred to as the Southern California Orthopedic Institute [SCOI] row) and a suture-bridge double-row (SB-DR) with Push-Locks have been shown to result in comparable improvement in treating rotator cuff tear, yet the biomechanical difference is unknown. The purpose of the current study was to determine whether a SCOI row repair had comparable initial biomechanical properties to a SB-DR repair.

Methods

Six matched pairs of fresh-frozen cadaveric shoulders with full-thickness supraspinatus tendon tears we created were included. Two different repairs were performed for each pair (SCOI row and SB-DR methods). Specimens were mounted on a material testing machine to undergo cyclic loading, which was cycled from 10 to 100 N at 1 Hz for 500 cycles. Construct gap formation was recorded at an interval of 50 cycles. Samples were then loaded to failure and modes of failure were recorded. Repeated-measures analysis of variance and pair-t test were used for statistical analyses.

Results

The construct gap formation did not differ between SCOI row and SB-DR repairs (P = 0.056). The last gap displacement was 1.93 ± 0.37 mm for SCOI row repair, and 1.49 ± 0.55 mm for SB-DR repair. The tensile load for 5 mm of elongation and ultimate failure were higher for SCOI row repair compared to SB-DR repair (P = 0.011 and 0.028, respectively). The ultimate failure load was 326.34 ± 11.52 N in the SCOI row group, and 299.82 ± 27.27 N in the SB-DR group. Rotator cuff repair with the SCOI row method failed primarily at the suture- tendon interface, whereas pullout of the lateral row anchors was the primary mechanism of failure for repair with the SB-DR method.

Conclusion

Rotator cuff repair with the SCOI row method has superior biomechanical properties when compared with the SB-DR method. Therefore, SCOI row repair using a medially-based single-row technique with triple-loaded suture anchor is recommended to improve the initial strength in treating full-thickness rotator cuff tears.
The effects of changes in distance to nearest health facility on under-5 mortality and health care utilization in rural Malawi, 1980–1998
Authors: Quattrochi John P. , Hill Kenneth , Salomon Joshua A. , Castro Marcia C.
Published: September 2020

Background

Despite important progress, the burden of under-5 mortality remains unacceptably high, with an estimated 5.3 million deaths in 2018. Lack of access to health care is a major risk factor for under-5 mortality, and distance to health care facilities has been shown to be associated with less access to care in multiple contexts, but few such studies have used a counterfactual approach to produce causal estimates.

Methods

We combined retrospective reports on 18,714 births between 1980 and 1998 from the 2000 Malawi Demographic and Health Survey with a 1998 health facility census that includes the date of construction for each facility, including 335 maternity or maternity/dispensary facilities built in rural areas between 1980 and 1998. We estimated associations between distance to nearest health facility and (i) under-5 mortality, using Cox proportional hazards models, and (ii) maternal health care utilization (antenatal visits prior to delivery, place of delivery, receiving skilled assistance during delivery, and receiving a check-up following delivery), using linear probability models. We also estimated the causal effect of reducing the distance to nearest facility on those outcomes, using a two-way fixed effects approach.

Findings

We found that greater distance was associated with higher mortality (hazard ratio 1.007 for one additional kilometer [95%CI 1.001 to 1.014]) and lower health care utilization (for one additional kilometer: 1.2 percentage point (pp) increase in homebirth [95%CI 0.8 to 1.5]; 0.8 pp. decrease in at least three antenatal visits [95% CI − 1.4 to − 0.2]; 1.2 pp. decrease in skilled assistance during delivery [95%CI − 1.6 to − 0.8]). However, we found no effects of a decrease in distance to the nearest health facility on the hazard of death before age 5 years, nor on antenatal visits prior to delivery, place of delivery, or receiving skilled assistance during delivery. We also found that reductions in distance decrease the probability that a woman receives a check-up following delivery (2.4 pp. decrease for a 1 km decrease [95%CI 0.004 to 0.044]).

Conclusion

Reducing under-5 mortality and increasing utilization of care in rural Malawi and similar settings may require more than the construction of new health infrastructure. Importantly, the effects estimated here likely depend on the quality of health care, the availability of transportation, the demand for health services, and the underlying causes of mortality, among other factors.
The similarity of inherited diseases (II): clinical and biological similarity between the phenotypic series
Authors: Gamba Alessio , Salmona Mario , Cantù Laura , Bazzoni Gianfranco
Published: September 2020

Background

Despite being caused by mutations in different genes, diseases in the same phenotypic series are clinically similar, as reported in Part I of this study. Here, in Part II, we hypothesized that the phenotypic series too might be clinically similar. Furthermore, on the assumption that gene mutations indirectly cause clinical phenotypes by directly affecting biological functions, we hypothesized that clinically similar phenotypic series might be biologically similar as well.

Methods

To test these hypotheses, we generated a clinical similarity network and a set of biological similarity networks. In both types of network, the nodes represent the phenotypic series, and the edges linking the nodes indicate the similarity of the linked phenotypic series. The weight of each edge is proportional to a similarity coefficient, which depends on the clinical phenotypes and the biological features that are shared by the linked phenotypic series, in the clinical and biological similarity networks, respectively.

Results

After assembling and analyzing the networks, we raised the threshold for the similarity coefficient, to retain edges of progressively greater weight. This way all the networks were gradually split into fragments, composed of phenotypic series with increasingly greater degrees of similarity. Finally, by comparing the fragments from the two types of network, we defined subsets of phenotypic series with varying types and degrees of clinical and biological correlation.

Conclusions

Like the individual diseases, the phenotypic series too are clinically and biologically similar to each other. Furthermore, our findings unveil different modalities of correlation between the clinical manifestations and the biological features of the inherited diseases.
Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis
Authors: Guan Yibing , Xu Fangshi , Wang Yiyuan , Tian Juanhua , Wan Ziyan , Wang Zhenlong , Chong Tie
Published: September 2020

Background

Circulating tumor cells (CTCs) play a key role in cancer progression, especially metastasis, due to the rarity and heterogeneity of CTCs, fewer researches have been conducted on them at the molecular level. However, through the Gene Expression Omnibus (GEO) database, this kind of minority researches can be well integrated, the gene expression differences between CTCs and primary tumors can be identified, and molecular targets for CTCs can be found.

Methods

We analyzed 7 sets of gene chips (GSE82198, GSE99394, GSE31023, GSE65505, GSE67982, GSE76250, GSE50746) obtained by GEO. Analysis of differentially expressed genes (DEGs) between CTCs and corresponding primary tumors by NetworkAnalyst. Metascape tool for Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential genes and visual display. Cytoscape performs protein-protein interaction (PPI) analysis and obtains the hub genes. Renal cancer patients’ clinical specimens to verify the correctness of enrichment results. Prognostic analysis of hub genes in kidney cancer patients using the Kaplan–Meier plotter survival analysis tool.

Results

We obtained a total of 589 DEGs. The GO / KEGG enrichment results indicate that the DEGs are mainly concentrated in cell adhesion, epithelial-mesenchymal transition (EMT), and apoptosis. Renal cancer clinical specimens suggest that CTCs have epithelial and mesenchymal types. At the same time, PSMC2 can be used as a poor prognostic indicator for renal cancer patients.

Conclusions

In summary, our study suggests that compared with primary tumors, CTCs mainly change cell adhesion, EMT, and apoptosis. PSMC2 can be used as a poor prognostic factor.
NNT-AS1 modulates prostate cancer cell proliferation, apoptosis and migration through miR-496/DDIT4 axis
Authors: Yao Changlei , Cheng Xianghua , Guo Xiuquan , Lu Xulou , Bu Fan , Xu Yanfen
Published: September 2020

Background

Emerging studies have disclosed long non-coding RNAs (lncRNAs) as pivotal modulators in the progression of prostate cancer (PCa). Current research planned to figure out the involvement of lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in PCa.

Methods

RNA expression was examined using RT-qPCR in PCa cells. Functional assays assessed the viability, proliferation, apoptosis and migration of PCa cells. RNA pull down and luciferase reporter experiments detected the interplay between miRNA and lncRNA or mRNA.

Results

NNT-AS1 was apparently upregulated in PCa cells. NNT-AS1 deficiency abrogated PCa cell viability, proliferation and migration but promoted apoptosis. Besides, miR-496 could be sequestered by NNT-AS1 to elevate the expression of DNA damage inducible transcript 4 (DDIT4) in PCa. Rescue assays indicated that overexpressed DDIT4 or restrained miR-496 could reverse the influence of NNT-AS1 depletion on malignant processes in PCa cells.

Conclusion

NNT-AS1 contributes to the malignant phenotypes of PCa cells through targeting miR-496 to boost DDIT4 expression.
Major complications of post-chemotherapy retroperitoneal lymph node dissection in a contemporary cohort of patients with testicular cancer and a review of the literature
Authors: Ruf Christian Guido , Krampe Simon , Matthies Cord , Anheuser Petra , Nestler Tim , Simon Jörg , Isbarn Hendrik , Dieckmann Klaus Peter
Published: September 2020

Background

Post-chemotherapy retroperitoneal lymph node dissection (pc-RPLND) is one cornerstone in the clinical management of patients with nonseminomatous testicular germ cell tumours (GCT). A wide range of complication rates in this type of surgery is reported so far. We retrospectively evaluated the frequency of major complications by using the Clavien-Dindo classification and analysed the influence of various clinical factors on complication rates in pc-RPLND.

Methods

We retrospectively analysed 146 GCT patients undergoing pc-RPLND. Complications of grade III–V according to the Clavien-Dindo classification occurring within 30 days after surgery were registered along with the following clinical factors: age, body mass index (BMI), duration of surgery, number of anatomic fields resected, side of primary tumour, histology of surgical specimen, histology of primary tumour, and total dose of cisplatin applied prior to surgery. For comparison, we also evaluated 35 chemotherapy-naïve patients with primary RPLND and 19 with laparoscopic RPLND. We analysed types and frequencies of the various complications as well as associations with clinical factors using descriptive statistical methods.

Results

A total of 14.4% grade III–IV complications were observed in pc-RPLND, and 8.6% and 5.3% in primary and in laparoscopic RPLND, respectively. There was no perioperative mortality. Lymphocele was the most frequent adverse event (16% of grade III–IV complications). Operation time > 270 min (p = 0.001) and vital cancer in the resected specimen (p = 0.02) were significantly associated with higher complication rates. Left-sided resection fields involved two-fold higher complication rates, barely missing statistical significance (p = 0.06).

Conclusions

Pc-RPLND involves a grade III–V complication rate of 14.4%. Prolonged operation time and vital cancer in the residual mass are significantly associated with higher complication rates. The Clavien-Dindo classification system may allow inter-observer variation in rating complication grades, which may represent one reason for the wide range of reported RPLND complication rates. RPLND represents major surgery and surgeons active in this field must be competent to manage adverse events.
Exploring the role of shift work in the self-reported health and wellbeing of long-term and assisted-living professional caregivers in Alberta, Canada
Authors: Awosoga Oluwagbohunmi , Steinke Claudia , Nord Christina , Doan Jon , Varsanyi Stephanie , Meadows Jeff , Odole Adesola , Murphy Sheli
Published: September 2020

Background

Numerous studies have found negative outcomes between shift work and physical, emotional, and mental health. Many professional caregivers are required to work shifts outside of the typical 9 am to 5 pm workday. Here, we explore whether shift work affects the health and wellbeing of long-term care (LTC) and assisted-living (AL) professional caregivers.

Method

The Caring for Professional Caregivers research study was conducted across 39 LTC and AL facilities in Alberta, Canada. Of the 1385 questionnaires distributed, 933 surveys (67.4%) were returned completed. After identifying 49 questions that significantly explained variances in the reported health status of caregivers, we examined whether there was a relationship between these questions and reported health status of caregivers working night shifts.

Results

We found significant differences between responses from those working different shifts across six of seven domains, including physical health, health conditions, mental/emotional health, quality of life, and health behaviors. In particular, we found that night shift caregivers were more likely to report incidents of poor heath (i.e., they lacked energy, had regular presences of neck and back pain, regular or infrequent incidents of fatigue or low energy, had difficulty falling asleep, and that they never do exercise) and less likely to report incidents of good health (i.e., did not expect their health to improve, were not satisfied with their health, do not have high self-esteem/were happy, were unhappy with their physical appearance, and do not get a good night’s sleep), compared to caregivers working other shifts.

Conclusions

Our study shows that professional caregivers working the night shift experience poor health status, providing further evidence that night shift workers’ health is at risk. In particular, caregivers reported negative evaluations of their physical, mental/emotional health, lower ratings of their quality of life, and negative responses to questions concerning whether they engage in healthy behaviors. Our findings can support healthcare stakeholders outline future policies that ensure caregivers are adequately supported so that they provide quality care.
Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery
Authors: Diboun Ilhame , Ramanjaneya Manjunath , Majeed Yasser , Ahmed Lina , Bashir Mohammed , Butler Alexandra E. , Abou-Samra Abdul Badi , Atkin Stephen L. , Mazloum Nayef A. , Elrayess Mohamed A.
Published: September 2020

Background

Pregnant women with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM) are at increased risks of pre-term labor, hypertension and preeclampsia. In this study, metabolic profiling of blood samples collected from GDM, T2DM and control pregnant women was undertaken to identify potential diagnostic biomarkers in GDM/T2DM and compared to pregnancy outcome.

Methods

Sixty-seven pregnant women (21 controls, 32 GDM, 14 T2DM) in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP®Quant 500 Kit. Linear regression models were used to identify the metabolic signature of GDM and T2DM, followed by generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine best predictors of GDM, T2DM and pre-term labor.

Results

The gestational age at delivery was 2 weeks earlier in T2DM compared to GDM and controls and correlated negatively with maternal HbA1C and systolic blood pressure and positively with serum albumin. Linear regression models revealed elevated glutamate and branched chain amino acids in GDM + T2DM group compared to controls. Regression models also revealed association of lower levels of triacylglycerols and diacylglycerols containing oleic and linoleic fatty acids with pre-term delivery. A generalized linear model ROC analyses revealed that that glutamate is the best predictors of GDM compared to controls (area under curve; AUC = 0.81). The model also revealed that phosphatidylcholine diacyl C40:2, arachidonic acid, glycochenodeoxycholic acid, and phosphatidylcholine acyl-alkyl C34:3 are the best predictors of GDM + T2DM compared to controls (AUC = 0.90). The model also revealed that the triacylglycerols C17:2/36:4 and C18:1/34:1 are the best predictors of pre-term delivery (≤ 37 weeks) (AUC = 0.84).

Conclusions

This study highlights the metabolite alterations in women in their second trimester with diabetes mellitus and identifies predictive indicators of pre-term delivery. Future studies to confirm these associations in other cohorts and investigate their functional relevance and potential utilization for targeted therapies are warranted.
Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome
Authors: Szczepanski Jamie , Spencer Shauna-Kay , Griffin Ashley , Bowles Teylor , Williams Jan Michael , Kyle Patrick B. , Dumas John Polk , Araji Sarah , Wallace Kedra
Published: September 2020

Background

The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20–40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome.

Methods

On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 μg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 μg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey’s test for post hoc analysis.

Results

Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34).

Conclusion

The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.
The immunomodulatory effect of cathelicidin-B1 on chicken macrophages
Authors: Peng Lianci , Scheenstra Maaike R. , van Harten Roel M. , Haagsman Henk P. , Veldhuizen Edwin J. A.
Published: September 2020

Cathelicidins (CATHs) play an important role in the innate immune response against microbial infections. Among the four chicken cathelicidins, CATH-B1 is studied the least. In this study, the effect of CATH-B1 on the macrophage response towards avian pathogenic E. coli (APEC) and bacterial ligands was investigated. Our results show that APEC induced CATH-B1 gene expression in both a chicken macrophage cell line (HD11 cells) and primary macrophages, while expression of the other three CATHs was virtually unaffected. While the antimicrobial activity of CATH-B1 is very low under cell culture conditions, it enhanced bacterial phagocytosis by macrophages. Interestingly, CATH-B1 downregulated APEC-induced gene expression of pro-inflammatory cytokines (IFN-β, IL-1β, IL-6 and IL-8) in primary macrophages. In addition, CATH-B1 pre-incubated macrophages showed a significantly higher gene expression of IL-10 after APEC challenge, indicating an overall anti-inflammatory profile for CATH-B1. Using isothermal titration calorimetry (ITC), CATH-B1 was shown to bind LPS. This suggests that CATH-B1 reduces toll like receptor (TLR) 4 dependent activation by APEC which may partly explain the decreased production of pro-inflammatory cytokines by macrophages. On the contrary, direct binding of CATH-B1 to ODN-2006 enhanced the TLR21 dependent activation of macrophages as measured by nitric oxide production. In conclusion, our results show for the first time that CATH-B1 has several immunomodulatory activities and thereby could be an important factor in the chicken immune response.
Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities
Authors: Lu Yeh-Lin , Lee Chia-Jung , Lin Shyr-Yi , Hou Wen-Chi
Published: September 2020

Background

The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro.

Results

The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro.

Conclusion

The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.
Computer and robotic – assisted total knee arthroplasty: a review of outcomes
Authors: Shatrov Jobe , Parker David
Published: September 2020

Background

Total knee arthroplasty (TKA) is a successful treatment for tricompartmental knee arthritis. Computer navigation and robotic-assisted-surgery (RAS) have emerged as tools that aim to help plan and execute surgery with greater precision and consistency. We reviewed the most current literature to describe the historical background and outcomes compared to conventional TKA.

Methods

A review and synthesis of the literature comparing the patient reported outcomes (PROM’s) of RA TKA and computer-assisted (CA) TKA to conventional TKA was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

CAS TKA improves accuracy and consistency of implant position, and appears to provide a small improvement in PROMs and implant survival compared to conventional TKA. RTKA similarly improves implant accuracy compared to conventional techniques and early results suggest a similar small benefit in PROMs compared to conventional TKA. A strengthening trend is emerging showing CAS TKA has greatest benefit to implant survival in people under 65. RTKA survival analysis data is more limited and early results do not allow strong conclusions, however early trends are similar to CAS TKA.

Conclusion

Results for CAS-TKA show improvement in alignment, and early clinical outcomes have revealed promising results, with longer-term data and medium-term survival analysis recently emerging showing small benefits over conventional TKA. RTKA represents another phase of development. Early results show similar trends to that of CAS TKA with longer-term data still to come.