bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate control with intravenous diltiazem, verapamil, and metoprolol in acute atrial fibrillation with rapid ventricular rate
Authors: Medeiros Tia , Bui Vi , Almekdash Mhd Hasan , Keesari Rohali , Lee Young R
Published: May 2021

Introduction:

Diltiazem is a preferred agent for rate control in atrial fibrillation due to its quick onset, minimal side effects, and low cost. Due to its intermittent national shortage since February 2018, the utilization of intravenous metoprolol and verapamil has increased. This study investigated the effect of intravenous diltiazem, metoprolol, and verapamil on rate control in patients with atrial fibrillation with rapid ventricular rate.

Methods:

This study was a retrospective, single-center, cohort study conducted in patients with acute atrial fibrillation receiving intravenous diltiazem, metoprolol, or verapamil for rapid ventricular rate between 1 January 2012 and 31 August 2018. The primary outcome was the incidence of patients who achieved a rate less than 100 bpm within 1 h of treatment. Secondary outcomes included time to achieve rate control, heart rate at 30 min and 1 h after administration, bradycardia and hypotension incidence, the requirement of other rate control agent(s), inpatient admission, length of stay, and mortality.

Results:

A total of 73 patients were included in the study. At 1 h after receiving the initial rate control drug, there was no statistically significant difference between diltiazem, metoprolol, and verapamil in achieving rate control. Median time to ventricular rate control was 166 min in the diltiazem group, 297 min in the metoprolol group, and 100.5 min in the verapamil group.

Conclusion:

There was no difference in achieving rate control when using intravenous diltiazem, metoprolol, or verapamil. Any of the three rate control agents may be used for rate control. However, further studies are needed to determine which agent is superior for rate control.
A rare case report of gemcitabine-induced thrombotic microangiopathies
Authors: Madkhali Mohammed Ali
Published: May 2021

A 65-year-old female patient with breast cancer and soft tissue sarcoma who experienced a gemcitabine-induced thrombotic microangiopathies manifestation visited the emergency department. The renal biopsy revealed endothelial cell swelling, focal reduplication of glomerular basement membrane, and narrowed capillary lumens with fibrin deposition and fragmented erythrocytes which are compatible with thrombotic microangiopathies. The patient was presented with organ injury, acute renal failure with the need for hemodialysis technique. The patient recovered after the appropriate treatment. Continuous observation of renal function during gemcitabine treatment regularly and withdrawal of treatment if acute kidney injury occurs is essential as acute kidney injury along with thrombotic microangiopathies may prove to be life-threatening.
Sticks and carrots for peace: The effect of manipulative mediation strategies on post-conflict stability
Authors: Ruhe Constantin , Volg Iris
Published: May 2021

Mediation is widely used to settle armed conflict and interstate crises. However, the debate over the most appropriate and effective mediation strategy is still ongoing. In particular, manipulative mediation is controversial, with some research indicating that heavy-handed mediation may buy short-term peace at the expense of an instable long-term situation. This paper re-evaluates these claims. We discuss how existing theoretical arguments either do not imply long-term instability or implicitly make unrealistic assumptions to explain possible long-term problems of manipulative strategies. We re-examine published empirical evidence for problematic long-term effects of manipulative mediation in interstate crises. We demonstrate statistically that this evidence actually implies a different conclusion and instead supports our theoretical argument: manipulative mediation is associated with substantively greater stability compared to unmediated cases, although this effect weakens and becomes statistically insignificant after several years. Interestingly, non-manipulative mediation appears to be uncorrelated with post-crisis stability, based on our analysis.
COVID-19 news reporting and engaging in the age of social media: Comparing Xinhua News Agency and The Paper
Authors: Chen Zenan , Xu Xiaoge
Published: May 2021

“To follow and to be followed” has become the new normal in news communication in the age of social media. News audience follow news via social media while they are being followed by news anytime anywhere. This new normal has created a pressing need to investigate whether social media have brought any changes to both party-controlled and market-oriented news media in China in reporting crises. Comparing Xinhua News Agency (party-controlled) and The Paper (market-oriented), this study investigated how they reported COVID-19 and how their news consumers engaged with their COVID-19 news stories on Jinri Toutiao, a popular and yet special form of social media. This study found that Xinhua News Agency continued to stay overwhelmingly positive, while The Paper was more neutral in reporting the health crisis. Xinhua News Agency was surprisingly more episodic than The Paper in framing the pandemic. The Paper, however, had a higher level of user engagement than Xinhua News Agency. To cater to the changing news-seeking behaviors and patterns, both party-controlled and market-oriented news media have changed their operations, but not their fundamental orientations.
Women offenders who served community sentences: A view from Catalonia
Authors: Vasilescu Cristina
Published: May 2021

Unlike in other jurisdictions, in Catalonia there has been no specific evaluation of women’s experiences regarding community sentences. The purpose of this article is to contribute to filling this gap by conducting qualitative research in Barcelona and Girona to analyse the experiences of women serving community sentences. To this end, 23 semi-structured interviews with women offenders are analysed. The results follow the trend found in research conducted in other jurisdictions and show that women have multiple issues, responsibilities and needs in comparison with men, and what works with female offenders is different from what works with male offenders with regard to supervision style, relationship with professionals and unpaid work or therapy environments. The findings make it possible to identify alternative responses that offer appropriate support and interventions to address women’s underlying problems and reduce reoffending. The article underscores the importance of listening to women’s voices in order to achieve a gender-sensitive criminal justice system.
The Development and Validation of the Social Enterprise of Science Index (SESI): An Instrument to Measure Grasp of the Social-Institutional Aspects of Science
Authors: Huxster Joanna K. , Slater Matthew H. , Landrum Asheley R.
Published: May 2021

Significant gaps remain between public opinion and the scientific consensus on many issues. We present the results of three studies ( N = 722 in total) for the development and testing of a novel instrument to measure a largely unmeasured aspect of scientific literacy: the enterprise of science, particularly in the context of its social structures. We posit that this understanding of the scientific enterprise is an important source for the public’s trust in science. Our results indicate that the Social Enterprise of Science Index (SESI) is a reliable and valid instrument that correlates positively with trust in science ( r = .256, p < .001), and level of education ( r = .245, p < .001). We also develop and validate a six question short version of the SESI for ease of use in longer surveys.
Placebo Effects: A New Theory
Authors: Liu Tao
Published: May 2021

Placebo effects have increasingly aroused scientific and public interest for their clinical and research values. However, underlying mechanisms of this mind–body phenomenon are not yet fully understood. In this article, I propose a new model according to which context-based placebo effects source from positive treatment beliefs but are directly caused by benefit expectations. By virtue of mediating belief-expectation transformation, placebo administration triggers, and thus has a pivotal role in, subsequent therapeutic responses.
Effects of Improv Training on Older Adults in a Long Term Care Facility
Authors: Lindquist Lee A. , Liggett Anna , Muhammad Ruqayyah , Seltzer Anne , Kim Kwang-Youn A. , Barish Becca , Wagner Abby , Ramirez-Zohfeld Vanessa
Published: May 2021

Adjusting to life in a long term care facility (LTCF) can be challenging for older adults. Improvisation (shortened to improv) is a unique activity that encourages creativity and adaptive cognitive stimulation, through performing short scenes with content suggestions. We sought to assess whether improv training, in the form of a course entitled Humor Doesn’t Retire (HDR), could impact patient-centered outcomes in a LTCF. About 15 adults (mean age 83.6 years) living in a LTCF participated in the 8-week HDR course with pre and 1-month post mixed method surveys assessing validated Patient Reported Outcomes Measurement Information System (PROMIS) measures and qualitative open-ended responses. Participants experienced significant improvements in social isolation and perceived stress ( p < .05), and trend improvements in positive affect, self-efficacy, and anxiety. Participants described themes of increased attentiveness, becoming more relaxed, increased cognitive stimulation, and improved communication skills. In conclusion, LTCFs may want to consider offering improv training to positively improve the lives of older adult residents.
Patellar Tendon Imbrication
Authors: Yalcin Sercan , Patel Ronak M. , Andrish Jack , Farrow Lutul D.
Published: May 2021

Background:

Patella alta is a common cause of patellar instability. Patellar tendon imbrication is a successful surgery addressing the deformity by shortening the patellar tendon without necessitating an osteotomy.

Indications:

Symptomatic patella alta causing patellar instability in both skeletally immature and adult patients.

Technique Description:

The patellar tendon is exposed, and levels of imbrication as determined preoperatively by radiographic measurements are outlined on the tendon with a marking pen. A third line is then made proximal to the level of dissection that is half the distance of the lengthening. From the distal marking, a flap of tendon, the anterior half, is elevated by sharp dissection using a fresh No. 15 blade proximal to the predetermined level. Next, “redundancy-reducing” 2-0 vicryl sutures are placed and left untied by entering at the proximal marking, passing deep to the tendon, and emerging at the middle of the intact posterior section of tendon, followed by placement of 3 structural #2 Ethibond/Ti-Cron horizontal sutures into the patellar tendon that will create and maintain the imbrication. These sutures are then tied proximally while applying downward pressure to the patella to avoid tying under tension. Next, the “redundancy-reducing” sutures are tied thus imbricating the redundant posterior section of tendon. In a “pants over vest” fashion, the distal end of the anterior section of isolated tendon is repaired with ‘‘0’’ absorbable suture. The knee is then flexed beyond 90° to assess competence of the suture lines and to assess the need for quadriceps lengthening.

Results:

Radiographic shortening is maintained at a minimum of 2 years on 27 patients/32 knees. There were no complications directly related to the technique.

Discussion/Conclusion:

Patellar tendon imbrication is a safe and effective procedure to correct patella alta in the setting of lateral patellar instability. On average, the technique allowed 1 cm of patellar tendon shortening and maintained the correction at a minimum 2-year follow-up. In the skeletally immature patient, this technique allows correction of patella alta by avoidance of a tibial tuberosity osteotomy.
Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences
Authors: Cornejo-Granados Fernanda , Kohl Thomas A. , Sotomayor Flor Vásquez , Andres Sönke , Hernández-Pando Rogelio , Hurtado-Ramirez Juan Manuel , Utpatel Christian , Niemann Stefan , Maurer Florian P. , Ochoa-Leyva Adrian
Published: May 2021

Background

Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense.

Results

We found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth.

Conclusions

This study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php).
Genome-wide association analysis reveals that EDNRB2 causes a dose-dependent loss of pigmentation in ducks
Authors: Xi Yang , Xu Qian , Huang Qin , Ma Shengchao , Wang Yushi , Han Chunchun , Zhang Rongping , Wang Jiwen , Liu Hehe , Li Liang
Published: May 2021

Background

Birds have various plumage color patterns, and spot is a common phenotype. Herein, we conducted genome-wide association studies (GWAS) in a population of 225 ducks with different sized black spots to reveal the genetic basis of this phenomenon.

Results

First, we quantified the black spot phenotype within the duck population. The results showed that the uncolored area of the body surface first appeared on the ventral side. With increasing duck age, the area of the black spots was highly conserved across the whole body surface. The GWAS results identified a 198 kb (Chr4: 10,149,651 bp to 10,348,068 bp) genetic region that was significantly associated with the black spot phenotype. The conditional GWAS and linkage disequilibrium (LD) analysis further narrowed the ultimate candidate region to 167 kb (Chr4: 10,180,939 bp to 10,348,068 bp). A key gene regulating melanoblast migration and differentiation, EDNRB2 (Endothelin B receptor-like), was found in the candidate region and having significant mRNA expression level changes in embryonic duck skin tissue with different spot sizes. The significant SNPs (single nucleotide polymorphisms) associated with the EDNRB2 gene were annotated, and two mutations (Chr4: 10,180,939 T > C and Chr4: 10,190,671 A > T) were found to result in the loss of binding sites for two trans-factors, XBP1 and cMYB. The phenotypic effect of these two mutations suggested that they can regulate the size of black spots in a dose-dependent manner, and Chr4: 10,180,939 T > C was the major allele locus.

Conclusions

Our results revealed that EDNRB2 was the gene responsible for the variation in duck body surface spot size. Chr4: 10,180,939 T > C was the major allele that explained 49.5 % (dorsal side) and 32.9 % (ventral side) of the variation in duck body surface spot size, while 32.1 % (dorsal side) and 19.1 % (ventral side) of the variation could be explained by Chr4: 10,190,671 A > T. The trans-factor prediction also suggested that XBP1 and cMYB have the potential to interact with EDNRB2, providing new insights into the mechanism of action of these genes.
Association between hearing loss and frailty: a systematic review and meta-analysis
Authors: Tian Rong , Almeida Osvaldo P. , Jayakody Dona M. P. , Ford Andrew H.
Published: May 2021

Background

Frailty is associated with poor health outcomes in later life. Recent studies suggested that hearing loss may be a potentially modifiable risk factor associated with frailty.

Methods

This systematic review and meta-analysis aimed to investigate the association between hearing loss and frailty in observational studies of adults aged 50 years or over. We included observational studies with participants ≥ 50 years old that have clear descriptions of hearing and frailty measurement methods. Meta-analyses were conducted using measurement of risk and 95 % confidence interval of each individual study. Quality assessment, risk of bias, heterogeneity and sensitivity analyses were also conducted. Our study followed PRISMA guidelines.

Results

Our search identified 4508 manuscripts published in English between 1 and 2000 and 9 February 2021. Sixteen articles reported acceptable measurements of both hearing loss and frailty. Two papers were not suitable for meta-analysis. Twelve sets of cross-sectional data involving 12,313 participants, and three sets of longitudinal data involving 3042 participants were used in the meta-analysis. Hearing loss was associated with an 87 % increase in the risk of frailty among cross-sectional studies (risk ratio [RR] 1.87; 95 %CI 1.63–2.13) and 56 % among longitudinal studies (RR 1.56; 95 %CI 1.29–1.88). There was considerable heterogeneity among studies, but their quality rating, sample size or approach used to assess hearing loss did not change the results substantially.

Conclusions

The findings of this systematic review and meta-analysis of observational studies suggest that hearing loss increases the risk of frailty in later life. Whether this relationship is causal remains to be determined.
Functional status and its associated factors among community-dwelling older adults in rural Nepal: findings from a cross-sectional study
Authors: Ghimire Saruna , Paudel Grish , Mistry Sabuj Kanti , Parvez Mahmood , Rayamajhee Binod , Paudel Pravash , Tamang Man Kumar , Yadav Uday Narayan
Published: May 2021

Background

The high burden of chronic conditions, coupled with various physical, mental, and psychosocial changes that accompany the phenomenon of aging, may limit the functional ability of older adults. This study aims to assess the prevalence of poor functional status and investigate factors associated with poor functional status among community-dwelling older adults in rural communities of eastern Nepal.

Methods

Data on 794 older adults aged ≥ 60 years from a previous community-based cross-sectional study was used. Participants were recruited from rural municipalities of Morang and Sunsari districts of eastern Nepal using multi-stage cluster sampling. Functional status was assessed in terms of participants’ ability to perform activities of daily living using the Barthel Index. Covariates included sociodemographic characteristics, lifestyle factors, and self-reported chronic conditions. A binary logistic regression model was used to investigate factors associated with poor functional status.

Results

The overall prevalence of poor functional status was 8.3 % (male: 7.0 % and female: 9.6 %), with most dependence noted for using stairs (17.3 %), followed by dressing (21.9 %) on Barthel Index. In the adjusted model, oldest age group (odds ratio [OR] = 2.83, 95 %CI: 1.46, 5.50), those unemployed (OR = 2.41, 95 %CI: 1.26, 4.65), having memory/concentration problems (OR = 2.32, 95 %CI: 1.30, 4.13), depressive symptoms (OR = 2.52, 95 %CI: 1.28, 4.95), and hypertension (OR = 1.78, 95 %CI: 1.03, 3.06) had almost or more than two times poor functioning.

Conclusions

One in 12 older adults had poor functional status as indicated by their dependency on the items of the Barthel Index; those in the oldest age bracket were more likely to exhibit poor functional status. We suggest future studies from other geographies of the country to supplement our study from the rural setting for comprehensive identification of the problem, which could guide the development of prevention strategies and comprehensive interventions for addressing the unmet needs of the older adults for improving functional status.
Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice
Authors: Hammad Ahmed , Zheng Zhao-Hong , Namani Akhileshwar , Elshaer Mohamed , Wang Xiu Jun , Tang Xiuwen
Published: May 2021

Background

The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis.

Methods

Azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software.

Results

Persistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified.

Conclusion

These findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation.

Graphical abstract
Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019
Authors: Zhou Linghui , Yu Qin , Wei Guoqing , Wang Linqin , Huang Yue , Hu Kejia , Hu Yongxian , Huang He
Published: May 2021

Background

Multiple myeloma (MM) is a major health concern. Understanding the different burden and tendency of MM in different regions is crucial for formulating specific local strategies. Therefore, we evaluated the epidemiologic patterns and explored the risk factors for MM death.

Methods

Data on MM were collected from the 2019 Global Burden of Disease study. We used incidence, mortality, and disability adjusted life-years to estimate the global, regional, and national burden of MM.

Results

In 2019, there were 155,688 (95% UI, 136,585 – 172,577) MM cases worldwide, of which 84,516 (54.3%, 70,924 – 94,910) were of men. The age-standardized incidence rate (ASIR) was 1.72/100,000 persons (95% UI, 1.59–1.93) in 1990 and 1.92/100,000 persons (95% UI, 1.68–2.12) in 2019. The number of MM deaths increased 1.19-fold from 51,862 (95% UI, 47,710–58,979) in 1990 to 113,474 (95% UI, 99,527 – 121,735) in 2019; the age-standardized death rate (ASDR) was 1.42/100,000 persons (95% UI, 1.24–1.52) in 2019. In recent 15 years, ASDR showed a steady tendency for men, and a downward tendency for women. Countries with high social-demographic indexes exhibited a higher ASIR and ASDR. Australasia, North America, and Western Europe had the highest ASIR and ASDR, with 46.3% incident cases and 41.8% death cases. Monaco had the highest ASIR and ASDR, which was almost half as high as the second highest country Barbados. In addition, United Arab Emirates and Qatar had the largest growth multiple in ASIR and ASDR, which was twice the third country Djibouti.

Conclusions

Globally, incident and death MM cases have more than doubled over the past 30 years. The increasing global burden may continue with population aging, whereas mortality may continue to decrease with the progression of medical technology. The global burden pattern of MM was diverse, therefore specific local strategies based on different burden patterns for MM are necessary.
Incidence trends in bladder and lung cancers between Denmark, Finland and Sweden may implicate oral tobacco (snuff/snus) as a possible risk factor
Authors: Hemminki Kari , Försti Asta , Hemminki Akseli , Ljungberg Börje , Hemminki Otto
Published: May 2021

Background

The dominant risk factor for urinary bladder cancer has been cigarette smoking, but, as smoking prevalence is decreasing in many populations, other risk factors may become uncovered. Such new risk factors could be responsible for halting the declining incidence of bladder cancer. We hypothesize that snuff use by Swedish men may increase the rate for bladder cancer, as snuff contains carcinogenic nitrosamines.

Methods

We carried out an ecological study by comparing incidence trends in lung and bladder cancers between Danish, Finnish and Swedish men in order to test if the Swedish bladder cancer rate deviates from the Danish and Finnish ones. We used the NORDCAN database for cancer data from 1960 through 2016 to test the hypothesis.

Results

In the three countries, the incidence of lung cancer started to decrease after a peak incidence, and this was later followed by declining incidence in bladder cancer in Denmark from 1990 to 2016 by 14.3%, in Finland by 8.3% but not in Sweden (the decline of 1.4% was not significant). The difference in trends can be partly explained by the increasing incidence in Swedish men aged 70 or more years. Sweden differs from the two other countries by low male smoking prevalence but increasing use of snuff recorded by various surveys.

Conclusion

The stable bladder cancer trend for Swedish men was opposite to the declining trends in Denmark, Finland and globally. We suggest that this unusual finding may be related to the increasing use of snuff by Swedish men. Average users of snuff are exposed to at least 3 times higher levels of carcinogenic tobacco-specific nitrosamines than a smoker of one daily pack of cigarettes.
DNA methylation signatures associated with prognosis of gastric cancer
Authors: Dai Jin , Nishi Akihiro , Li Zhe-Xuan , Zhang Yang , Zhou Tong , You Wei-Cheng , Li Wen-Qing , Pan Kai-Feng
Published: May 2021

Background

Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study.

Methods

Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression.

Results

We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed.

Conclusions

We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.
Risk factors associated with scabies infestation among primary schoolchildren in a low socio-economic area in southeast of Iran
Authors: Sanei-Dehkordi Alireza , Soleimani-Ahmadi Moussa , Zare Mehdi , Jaberhashemi Seyed Aghil
Published: May 2021

Background

Scabies is a neglected tropical disease caused by the mite Sarcoptes scabiei that burrows under the skin. It is a major health problem in tropical areas, largely affecting children. Scabies is common and highly contagious and in schoolchildren spreads quite rapidly, due to overcrowding and close contact within the schools. This study aimed to determine the risk factors associated with scabies infestation among primary schoolchildren in Bashagard County, one of the low socio-economic areas in southeast of Iran.

Methods

To conduct this community-based, descriptive, and cross-sectional study, four primary schools were randomly selected in the Bashagard County. All students in these schools were selected and examined for scabies. Clinical examination and sociodemographic profile of students were assessed using a pre-tested structured questionnaire. Chi-square test, and binary logistic regression were used to analyse the factors associated with scabies infestation by SPSS version 21 software.

Results

Out of 480 studied schoolchildren, 15 cases of scabies with a prevalence of 3.1 % were observed. The frequency of infestation in males was 1.6 % and it was 4.7 % in females. Independent factors associated with a high risk of scabies infestation in unadjusted analysis were being student of grade 5–6 (cOR = 13.12, 95 % CI 2.92–58.89, p = 0.0001), low educational level of father (cOR = 4.37, 95 % CI 0.97–19.59, p = 0.036), low educational level of mother (cOR = 4.14, 95 % CI 1.92–18.57, p = 0.045), joblessness of father (cOR = 14.77, 95 % CI 4.97–43.89, p = 0.0001), employment of mother (cOR = 5.28, 95 % CI 1.38–20.16, p = 0.007), large family size (cOR = 3.34, 95 % CI 1.05–10.64, p = 0.031), use of shared articles (cOR = 33.37, 95 % CI 10.82–102.90, p = 0.0001), and absence of bathroom in the house (cOR = 11.77, 95 % CI 2.16–63.94, p = 0.0001).

Conclusions

Results of this study confirmed that scabies is still one of the most important health problems in the primary schools of the Bashagard County. Low socioeconomic status and personal hygiene of the schoolchildren were the most important factors influencing the prevalence of scabies. Improvement of socioeconomic conditions and implementation of appropriate educational programs and active surveillance system to quickly detect and treat scabies cases are necessary in order to reduce the prevalence of scabies in schoolchildren in this area.
High cytotoxicity of betulin towards fish and murine fibroblasts: Is betulin safe for nonneoplastic cells?
Authors: Małaczewska Joanna , Kaczorek-Łukowska Edyta , Kazuń Barbara
Published: May 2021

Background

Betulin, a natural pentacyclic triterpene with the lupane structure that is present in significant amounts in the outer bark of birch, is known for its broad array of biological and pharmacological properties. Betulin has attracted attention as a potential, natural-origin antimicrobial substance. The literature describes it as selectively toxic to neoplastic cells but safe for normal cells.

The research aim was to evaluate the basal cytotoxicity of betulin towards fish (BF-2) and murine (NIH/3T3) fibroblasts. We used four colorimetric tests that provide a preliminary evaluation of possible mechanisms of the cytotoxicity of a compound to assess the degree of the toxicity of betulin after 24, 48 and 72 h of incubation with cells: the MTT assay (mitochondrial activity assessment), the NRU assay (lysosomal membrane integrity assessment), the LDH assay (cellular membrane integrity assessment) and the SRB assay (total cellular protein content determination).

Results

The results revealed an exceptionally high sensitivity of mitochondria to the effect of betulin, with the other endpoints being less sensitive. Although murine fibroblasts were more vulnerable to the toxic effect of betulin than fish fibroblasts, the betulin CC50 values for both cell lines were comparable with analogous IC50 values determined by other researchers in studies involving cancerous cells.

Conclusions

The results indicate the need to verify the claim about the selective toxicity of betulin towards malignant cells and to conduct safety/toxicity tests before any potential therapeutic use of betulin in veterinary medicine.
Long non-coding RNAs in Epstein–Barr virus-related cancer
Authors: Liu Yitong , Hu Zhizhong , Zhang Yang , Wang Chengkun
Published: May 2021

Epstein Barr-virus (EBV) is related to several cancers. Long non-coding RNAs (lncRNAs) act by regulating target genes and are involved in tumourigenesis. However, the role of lncRNAs in EBV-associated cancers is rarely reported. Understanding the role and mechanism of lncRNAs in EBV-associated cancers may contribute to diagnosis, prognosis and clinical therapy in the future. EBV encodes not only miRNAs, but also BART lncRNAs during latency and the BHLF1 lncRNA during both the latent and lytic phases. These lncRNAs can be targeted regulate inflammation, invasion, and migration and thus tumourigenesis. The products of EBV also directly and indirectly regulate host lncRNAs, including LINC00312, NORAD CYTOR, SHNG8, SHNG5, MINCR, lncRNA-BC200, LINC00672, MALATI1, LINC00982, LINC02067, IGFBP7‐AS1, LOC100505716, LOC100128494, NAG7 and RP4-794H19.1, to facilitate tumourigenesis using different mechanisms. Additionally, lncRNAs have been previously validated to interact with microRNAs (miRNAs), and lncRNAs and miRNAs mutually suppress each other. The EBV-miR-BART6-3p/LOC553103/STMN1 axis inhibits EBV-associated tumour cell proliferation. Additionally, H. pylori–EBV co-infection promotes inflammatory lesions and results in EMT. HPV–EBV co-infection inhibits the transition from latency to lytic replication. KSHV–EBV co-infection aggravates tumourigenesis in huNSG mice. COVID-19–EBV co-infection may activate the immune system to destroy a tumour, although this situation is rare and the mechanism requires further confirmation. Hopefully, this information will shed some light on tumour therapy strategies tumourigenesis. Additionally, this strategy benefits for infected patients by preventing latency to lytic replication. Understanding the role and expression of lnRNAs in these two phases of EBV is critical to control the transition from latency to the lytic replication phase. This review presents differential expressed lncRNAs in EBV-associated cancers and provides resources to aid in developing superior strategies for clinical therapy.
Sharing power in global health research: an ethical toolkit for designing priority-setting processes that meaningfully include communities
Authors: Pratt Bridget
Published: May 2021

To promote social justice and equity, global health research should meaningfully engage communities throughout projects: from setting agendas onwards. But communities, especially those that are considered disadvantaged or marginalised, rarely have a say in the priorities of the research projects that aim to help them. So far, there remains limited ethical guidance and resources on how to share power with communities in health research priority-setting. This paper presents an“ethical toolkit”for academic researchers and their community partners to use to design priority-setting processes that meaningfully include the communities impacted by their projects. An empirical reflective equilibrium approach was employed to develop the toolkit. Conceptual work articulated ethical considerations related to sharing power in g0l0o0bal health research priority-setting, developed guidance on how to address them, and created an initial version of the toolkit. Empirical work (51 in-depth interviews, 1 focus group, 2 case studies in India and the Philippines) conducted in 2018 and 2019 then tested those findings against information from global health research practice. The final ethical toolkit is a reflective project planning aid. It consists of 4 worksheets (Worksheet 1- Selecting Partners; Worksheet 2- Deciding to Partner; Worksheet 3- Deciding to Engage with the Wider Community; Worksheet 4- Designing Priority-setting) and a Companion Document detailing how to use them. Reflecting on and discussing the questions in Worksheets 1 to 4 before priority-setting will help deliver priority-setting processes that share power with communities and projects with research topics and questions that more accurately reflect their healthcare and system needs.
An analysis of the impact of newborn survival policies in Pakistan using a policy triangle framework
Authors: Ahmed Jamil , Schneider Carmen Huckel , Alam Ashraful , Raynes-Greenow Camille
Published: May 2021

Introduction

Pakistan has made slow progress towards reducing the newborn mortality burden; as a result, it has the highest burden of newborn mortality worldwide. This article presents an analysis of the current policies, plans, and strategies aimed at reducing the burden of newborn death in Pakistan for the purpose of identifying current policy gaps and contextual barriers towards proposing policy solutions for improved newborn health.

Methods

We begin with a content analysis of federal-level policies that address newborn mortality within the context of health system decentralization over the last 20 years. This is then followed by a case study analysis of policy and programme responses in a predominantly rural province of Pakistan, again within the context of broader health system decentralization. Finally, we review successful policies in comparable countries to identify feasible and effective policy choices that hold promise for implementation in Pakistan, considering the policy constraints we have identified.

Results

The major health policies aimed at reduction of newborn mortality, following Pakistan’s endorsement of global newborn survival goals and targets, lacked time-bound targets. We found confusion around roles and responsibilities of institutions in the implementation process and accountability for the outcomes, which was exacerbated by an incomplete decentralization of healthcare policy-making and health service delivery, particularly for women around birth, and newborns. Such wide gaps in the areas of target-setting, implementation mechanism, and evaluation could be because the policy-making largely ignored international commitments and lessons of successful policy-making in comparable regional counties.

Conclusions

Inclusion of clear goals and targets in newborn survival policies and plans, completion of the decentralization process of maternal and child healthcare service delivery, and policy-making and implementation by translating complex evidence and using regional but locally applicable case studies will be essential to any effective policy-making on newborn survival in Pakistan.
Theory-based approach to developing an implementation plan to support the adoption of a patient decision aid for Down syndrome prenatal screening
Authors: Agbadjé Titilayo Tatiana , Menear Matthew , Gagnon Marie-Pierre , Légaré France
Published: May 2021

Background

Our team has developed a decision aid to help pregnant women and their partners make informed decisions about Down syndrome prenatal screening. However, the decision aid is not yet widely available in Quebec’s prenatal care pathways.

Objective

We sought to identify knowledge translation strategies and develop an implementation plan to promote the use of the decision aid in prenatal care services in Quebec, Canada.

Methods

Guided by the Knowledge-to-Action Framework and the Theoretical Domains Framework, we performed a synthesis of our research (11 publications) on prenatal screening in Quebec and on the decision aid. Two authors independently reviewed the 11 articles, extracted information, and mapped it onto the Knowledge-to-Action framework. Using participatory action research methods, we then recruited pregnant women, health professionals, managers of three prenatal care services, and researchers to (a) identify the different clinical pathways followed by pregnant women and (b) select knowledge translation strategies for a clinical implementation plan. Then, based on all the information gathered, the authors established a consensus on strategies to include in the plan.

Results

Our knowledge synthesis showed that pregnant women and their partners are not sufficiently involved in the decision-making process about prenatal screening and that there are numerous barriers and facilitators of the use of the decision aid in clinical practice (e.g., low intention to use it among health providers). Using a participatory action approach, we met with five pregnant women, three managers, and six health professionals. They informed us about three of Quebec’s prenatal care pathways and helped us identify 20 knowledge translation strategies (e.g., nurse discusses decision aid with women before they meet the doctor) to include in a clinical implementation plan. The research team reached a consensus about the clinical plan and also about broader organizational strategies, such as training healthcare providers in the use of the decision aid, monitoring its impact (e.g., measure decisional conflict) and sustaining its use (e.g., engage key stakeholders in the implementation process).

Conclusion

Next steps are to pilot our implementation plan while further identifying global strategies that target institutional, policy, and systemic supports for implementation.
Fast and efficient Rmap assembly using the Bi-labelled de Bruijn graph
Authors: Mukherjee Kingshuk , Rossi Massimiliano , Salmela Leena , Boucher Christina
Published: May 2021

Genome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there are very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary software that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics’ Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as rmapper, and compare its performance against the assembler of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) and Solve by Bionano Genomics on data from three genomes: E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was able to successfully run on all three genomes. The method of Valouev et al. (Proc Natl Acad Sci USA 103(43):15770–15775, 2006) only successfully ran on E. coli. Moreover, on the human genome rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies. Our software, rmapper is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/Rmapper.
Case report: a step-wise management of concurrent presentation of congenital single lung and aberrant right subclavian artery in an infant girl
Authors: Park Keon Young , Janek Kevin C. , Hermsen Joshua L. , Anagnostopoulos Petros V. , Le Hau D.
Published: May 2021

Introduction

Congenital single lung (CSL) is a rare condition, and symptomatic patients often present with respiratory distress or recurrent respiratory infection due to mediastinal shift causing vascular or airway compression. Aberrant right subclavian artery (ARSA) is another rare congenital anomality that can lead to tracheal or esophageal compressions. There is only one other case of concurrent presentation of CSL and ARSA reported, which presented unique challenge in surgical management of our patient. Here we present a step-wise, multidisciplinary approach to manage symptomatic CSL and ARSA.

Case presentation

An infant girl with a prenatal diagnosis of CSL developed worsening stridor and several episodes of respiratory illnesses at 11 months old. Cross-sectional imaging and bronchoscopic evaluation showed moderate to severe distal tracheomalacia with anterior and posterior tracheal compression resulting from severe mediastinal rotation secondary to right-sided CSL. It was determined that her tracheal compression was mainly caused by her aortic arch wrapping around the trachea, with possible additional posterior compression of the esophagus by the ARSA. She first underwent intrathoracic tissue expander placement, which resulted in immediate improvement of tracheal compression. Two days later, she developed symptoms of dysphagia lusoria due to increased posterior compression of her esophagus by the ARSA. She underwent transposition of ARSA to the right common carotid with immediate resolution of dysphagia lusoria. As the patient grew, additional saline was added to the tissue expander due to recurrence in compressive symptoms.

Conclusions

Concurrent presentation of CSL and ARSA is extremely rare. Asymptomatic CSL and ARSA do not require surgical interventions. However, if symptomatic, it is crucial to involve a multidisciplinary team for surgical planning and to take a step-wise approach as we were able to recognize and address both tracheomalacia and dysphagia lusoria in our patient promptly.