bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergent pancreatectomy for neoplastic disease: outcomes analysis of 534 ACS-NSQIP patients
Authors: Driedger Michael R. , Puig Carlos A. , Thiels Cornelius A. , Bergquist John R. , Ubl Daniel S. , Habermann Elizabeth B. , Grotz Travis E. , Smoot Rory L. , Nagorney David M. , Cleary Sean P. , Kendrick Michael L. , Truty Mark J.
Published: July 2020

Background

While emergent pancreatic resection for trauma has been previously described, no large contemporary investigations into the frequency, indications, and outcomes of emergent pancreatectomy (EP) secondary to complications of neoplastic disease exist. Modern perioperative outcomes data are currently unknown.

Methods

ACS-NSQIP was reviewed for all non-traumatic pancreatic resections (DP – distal pancreatectomy, PD - pancreaticoduodenectomy, or TP- total pancreatectomy) in patients with pancreatico-biliary or duodenal-ampullary neoplasms from 2005 to 2013. Patients treated for complications of pancreatitis were specifically excluded. Emergent operation was defined as NSQIP criteria for emergent case and one of the following: ASA Class 5, preoperative ventilator dependency, preoperative SIRS, sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Chi-square tests, Fisher’s exact tests were performed to compare postoperative outcomes between emergent and elective cases as well as between pancreatectomy types.

Results

Of 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients who underwent emergent resection. Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation. PD was performed in 409 (77%) patients, DP in 115 (21%), and TP in 10 (2%) patients. Overall major morbidity was significantly higher (46.1% vs. 25.6%,p < 0.001) for emergent vs. elective operations. Emergent operations resulted in increased transfusion rates (47.6% vs. 23.4%,p < 0.001), return to OR (14.0% vs. 5.6%,p < 0.001), organ-space infection (14.6 vs. 10.5,p = 0.002), unplanned intubation (9.% vs. 4.1%,p < 0.001), pneumonia (9.6% vs. 4.2%,p < 0.001), length of stay (14 days vs. 8 days,p < 0.001), and discharge to skilled facility (31.1% vs. 13.9%). These differences persisted when stratified by pancreatic resection type. The 30-day operative mortality was higher in the emergent group (9.4%vs. 2.7%,p < 0.001) and highest for emergent TP (20%).

Conclusion

Emergent pancreatic resection is markedly uncommon in the setting of neoplastic disease. Although these operations result in increased morbidity and mortality compared to elective resections, they can be life-saving in specific circumstances. The results of this large series of modern era national data may assist surgeons as well as patients and their families in making critical decisions in select cases of acutely complicated neoplastic disease.
Ethical and social implications of approaching death prediction in humans - when the biology of ageing meets existential issues
Authors: Gaille Marie , Araneda Marco , Dubost Clément , Guillermain Clémence , Kaakai Sarah , Ricadat Elise , Todd Nicolas , Rera Michael
Published: July 2020

Background

The discovery of biomarkers of ageing has led to the development of predictors of impending natural death and has paved the way for personalised estimation of the risk of death in the general population. This study intends to identify the ethical resources available to approach the idea of a long-lasting dying process and consider the perspective of death prediction. The reflection on human mortality is necessary but not sufficient to face this issue. Knowledge about death anticipation in clinical contexts allows for a better understanding of it. Still, the very notion of prediction and its implications must be clarified. This study outlines in a prospective way issues that call for further investigation in the various fields concerned: ethical, psychological, medical and social.

Methods

The study is based on an interdisciplinary approach, a combination of philosophy, clinical psychology, medicine, demography, biology and actuarial science.

Results

The present study proposes an understanding of death prediction based on its distinction with the relationship to human mortality and death anticipation, and on the analogy with the implications of genetic testing performed in pre-symptomatic stages of a disease. It leads to the identification of a multi-layered issue, including the individual and personal relationship to death prediction, the potential medical uses of biomarkers of ageing, the social and economic implications of the latter, especially in regard to the way longevity risk is perceived.

Conclusions

The present study work strives to propose a first sketch of what the implications of death prediction as such could be - from an individual, medical and social point of view. Both with anti-ageing medicine and the transhumanist quest for immortality, research on biomarkers of ageing brings back to the forefront crucial ethical matters: should we, as human beings, keep ignoring certain things, primarily the moment of our death, be it an estimation of it? If such knowledge was available, who should be informed about it and how such information should be given? Is it a knowledge that could be socially shared?
Metabolic engineering of Escherichia coli for optimized biosynthesis of nicotinamide mononucleotide, a noncanonical redox cofactor
Authors: Black William B. , Aspacio Derek , Bever Danielle , King Edward , Zhang Linyue , Li Han
Published: July 2020

Background

Noncanonical redox cofactors are emerging as important tools in cell-free biosynthesis to increase the economic viability, to enable exquisite control, and to expand the range of chemistries accessible. However, these noncanonical redox cofactors need to be biologically synthesized to achieve full integration with renewable biomanufacturing processes.

Results

In this work, we engineered Escherichia coli cells to biosynthesize the noncanonical cofactor nicotinamide mononucleotide (NMN+), which has been efficiently used in cell-free biosynthesis. First, we developed a growth-based screening platform to identify effective NMN+ biosynthetic pathways in E. coli. Second, we explored various pathway combinations and host gene disruption to achieve an intracellular level of ~ 1.5 mM NMN+, a 130-fold increase over the cell’s basal level, in the best strain, which features a previously uncharacterized nicotinamide phosphoribosyltransferase (NadV) from Ralstonia solanacearum. Last, we revealed mechanisms through which NMN+ accumulation impacts E. coli cell fitness, which sheds light on future work aiming to improve the production of this noncanonical redox cofactor.

Conclusion

These results further the understanding of effective production and integration of NMN+ into E. coli. This may enable the implementation of NMN+-directed biocatalysis without the need for exogenous cofactor supply.
Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya
Authors: Redmond Lawrence S. , Ogwang Martin D. , Kerchan Patrick , Reynolds Steven J. , Tenge Constance N. , Were Pamela A. , Kuremu Robert T. , Masalu Nestory , Kawira Esther , Otim Isaac , Legason Ismail D. , Dhudha Herry , Ayers Leona W. , Bhatia Kishor , Goedert James J. , Mbulaiteye Sam M.
Published: July 2020

Background

Endemic Burkitt lymphoma (eBL) is an aggressive B cell non-Hodgkin lymphoma associated with antigenic stimulation from Plasmodium falciparum malaria. Whether eBL risk is related to malaria parasite density is unknown. To address this issue, children with eBL, asymptomatic and clinical malaria, as a surrogate of malaria parasite density, were assessed.

Methods

Malaria-related laboratory results (parasite density, haemoglobin, platelet count, and white cell count [WBC]) count) were compiled for 4019 eBL cases and 80,532 subjects evaluated for asymptomatic malaria or clinical malaria (severe malaria anaemia, hyperparasitaemia, cerebral malaria, malaria prostration, moderate malaria, and mild malaria) in 21 representative studies published in Africa (mostly East Africa) and 850 eBL cases and 2878 controls with primary data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) case–control study in Uganda, Tanzania, and Kenya. The average values of malaria-related laboratory results were computed by condition and trends across single-year age groups were assessed using regression and spline models.

Results

Overall, malaria infection or malaria was diagnosed in 37,089 of children compiled from the literature. Children with eBL and asymptomatic parasitaemia/antigenaemia, but not those with clinical malaria, were closest in their mean age (age 7.1–7.2 vs. 7.4–9.8 years), haemoglobin level (10.0–10.4 vs. 11.7–12.3 g/dL), malaria parasite density (2800 vs. 1827–7780 parasites/µL), platelet count (347,000–353,000 vs. 244,000–306,000 platelets/µL), and WBC count (8180–8890 vs. 7100–7410 cells/µL). Parasite density in these two groups peaked between four to five years, then decreased steadily thereafter; conversely, haemoglobin showed a corresponding increase with age. Children with clinical malaria were markedly different: all had an average age below 5 years, had dramatically elevated parasite density (13,905–869,000 parasites/µL) and dramatically decreased platelet count (< 159,000 platelets/µL) and haemoglobin (< 7 g/dL).

Conclusions

eBL and asymptomatic parasitaemia/antigenaemia, but not clinical malaria, were the most similar conditions with respect to mean age and malaria-related laboratory results. These results suggest that children with asymptomatic parasitaemia/antigenaemia may be the population at risk of eBL.
Prediction of hospital visits for the general inpatient care using floating catchment area methods: a reconceptualization of spatial accessibility
Authors: Bauer J. , Klingelhöfer D. , Maier W. , Schwettmann L. , Groneberg D. A.
Published: July 2020

Background

The adequate allocation of inpatient care resources requires assumptions about the need for health care and how this need will be met. However, in current practice, these assumptions are often based on outdated methods (e.g. Hill-Burton Formula). This study evaluated floating catchment area (FCA) methods, which have been applied as measures of spatial accessibility, focusing on their ability to predict the need for health care in the inpatient sector in Germany.

Methods

We tested three FCA methods (enhanced (E2SFCA), modified (M2SFCA) and integrated (iFCA)) for their accuracy in predicting hospital visits regarding six medical diagnoses (atrial flutter/fibrillation, heart failure, femoral fracture, gonarthrosis, stroke, and epilepsy) on national level in Germany. We further used the closest provider approach for benchmark purposes. The predicted visits were compared with the actual visits for all six diagnoses using a correlation analysis and a maximum error from the actual visits of ± 5%, ± 10% and ± 15%.

Results

The analysis of 229 million distances between hospitals and population locations revealed a high and significant correlation of predicted with actual visits for all three FCA methods across all six diagnoses up to ρ = 0.79 (p < 0.001). Overall, all FCA methods showed a substantially higher correlation with actual hospital visits compared to the closest provider approach (up to ρ = 0.51; p < 0.001). Allowing a 5% error of the absolute values, the analysis revealed up to 13.4% correctly predicted hospital visits using the FCA methods (15% error: up to 32.5% correctly predicted hospital). Finally, the potential of the FCA methods could be revealed by using the actual hospital visits as the measure of hospital attractiveness, which returned very strong correlations with the actual hospital visits up to ρ = 0.99 (p < 0.001).

Conclusion

We were able to demonstrate the impact of FCA measures regarding the prediction of hospital visits in non-emergency settings, and their superiority over commonly used methods (i.e. closest provider). However, hospital beds were inadequate as the measure of hospital attractiveness resulting in low accuracy of predicted hospital visits. More reliable measures must be integrated within the proposed methods. Still, this study strengthens the possibilities of FCA methods in health care planning beyond their original application in measuring spatial accessibility.
Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis
Authors: Shang Anquan , Gu Chenzheng , Wang Weiwei , Wang Xuan , Sun Junjun , Zeng Bingjie , Chen Chen , Chang Wenjing , Ping Yili , Ji Ping , Wu Junlu , Quan Wenqiang , Yao Yiwen , Zhou Yongxin , Sun Zujun , Li Dong
Published: July 2020

Background

Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.

Methods

CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.

Results

Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.

Conclusion

Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.
Utility value estimates in cardiovascular disease and the effect of changing elicitation methods: a systematic literature review
Authors: Betts Marissa Blieden , Rane Pratik , Bergrath Evelien , Chitnis Madhura , Bhutani Mohit Kumar , Gulea Claudia , Qian Yi , Villa Guillermo
Published: July 2020

Objective

Identify the most recent utility value estimates for cardiovascular disease (CVD) via systematic literature review (SLR) and explore trends in utility elicitation methods in the last 6 years.

Methods

This SLR was updated on January 25, 2018, and identified studies reporting utilities for myocardial infarction (MI), stroke, angina, peripheral artery disease (PAD), and any-cause revascularization by searching Embase, PubMed, Health Technology Assessment Database, and grey literature.

Results

A total of 375 studies reported CVD utilities (pre-2013 vs post-2013: MI, 38 vs 32; stroke, 86 vs 113; stable angina, 8 vs 9; undefined/unstable angina, 23 vs 8; PAD, 29 vs 13; revascularization, 54 vs 40). Median average utilities for MI, stroke, and revascularization increased over time (pre-2013 vs post-2013: MI, 0.71 vs 0.79; stroke, 0.63 vs 0.64; revascularization, 0.76 vs 0.81); angina and PAD showed a decrease in median values over time (stable angina, 0.83 vs 0.72; undefined/unstable angina, 0.70 vs 0.69; PAD, 0.76 vs 0.71). The proportion of utility estimates from trials increased across health states (pre-2013 vs post-2013: 22.5% vs 37.2%), as did the proportion of trials using the EuroQol Five Dimensions Questionnaire (EQ-5D; pre-2013 vs post-2013: 73.8% vs 91.4%). Use of methods such as the standard gamble, time trade-off, and Health Utilities Index has declined.

Conclusions

Health state utilities for cardiovascular health states have changed in the last 6 years, likely due to changes in the types of studies conducted, the patient populations evaluated, and possibly changing utility elicitation methods. The EQ-5D has been used more frequently.
Male involvement in reproductive, maternal, newborn, and child health: evaluating gaps between policy and practice in Uganda
Authors: Gopal Prerna , Fisher Duncan , Seruwagi Gloria , Taddese Henock B.
Published: July 2020

Introduction

Male involvement in maternal and child health is a practice wherein fathers and male community members actively participate in caring for women and supporting their family to access better health services. There is positive association between male involvement and better maternal and child health outcomes. However, the practice is not always practiced optimally, especially in low- and middle-income countries, where women may not have access to economic resources and decision-making power.

Aim

This study investigates how key stakeholders within the health system in Uganda engage with the ‘male involvement’ agenda and implement related policies. We also analyzed men’s perceptions of male involvement initiatives, and how these are influenced by different political, economic, and organizational factors.

Methodology

This is a qualitative study utilizing data from 17 in-depth interviews and two focus group discussions conducted in Kasese and Kampala, Uganda. Study participants included men involved in a maternal health project, their wives, and individuals and organizations working to improve male involvement; all purposively selected.

Result

Through thematic analysis, four major themes were identified: ‘gaps between policy and practice’, ‘resources and skills’, ‘inadequate participation by key actors’, and ‘types of dissemination’. These themes represent the barriers to effective implementation of male involvement policies. Most health workers interviewed have not been adequately trained to provide male-friendly services or to mobilize men. Interventions are highly dependent on external aid and support, which in turn renders them unsustainable. Furthermore, community and religious leaders, and men themselves, are often left out of the design and management of male involvement interventions. Finally, communication and feedback mechanisms were found to be inadequate.

Conclusion

To enable sustainable behavior change, we suggest a ‘bottom-up’ approach to male involvement that emphasizes solutions developed by or in tandem with community members, specifically, fathers and community leaders who are privy to the social norms, structures, and challenges of the community.
Stigma: how it affects the substance use disorder patient
Authors: Zwick Janet , Appleseth Hannah , Arndt Stephan
Published: July 2020

The stigma surrounding individuals who have substance use disorders is a pervasive phenomenon that has had detrimental effects on treatment outcomes, health care providers, treatments, research, policies, and society as a whole (Kelly JF, Dow SJ, Westerhoff C , J Drug Issues_40:805-818, Kelly JF, Westerhoff, Int J Drug Policy_21:202-207, 2010). Stigma can be cultivated by various sources, but this article specifically focuses on the impact words have. Individuals influence each other through dynamic language processes. Language, which we use to communicate, represents shared values, history, beliefs, and customs. Moreover, language can be used to promote stigma or decrease it [Snodgrass S: The Power of Words: Changing the Language of Addiction, 2920]. Language usage for addiction medical care is dated in comparison to other standards. Research and organizations are recognizing that substance use treatment, policies, and language need to evolve to aid this crisis and those affected by this disease. Language sustains the stigma surrounding substance use. The stigmatized language used to describe substance use behaviors, individuals with substance use disorders, and substance use treatment can create barriers in essential areas, such as health care, employment, insurance policies, and laws for individuals who are trying to heal and make meaningful contributions to society. There are many ways to contribute to a more accepting society, but it starts with bottom-up processes like language choices in day-to-day conversations. An effort must be made to normalize destigmatized language when referring to substance use and individuals with substance use disorders.
Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies
Authors: He Yonghan , Khan Sajid , Huo Zhiguang , Lv Dongwen , Zhang Xuan , Liu Xingui , Yuan Yaxia , Hromas Robert , Xu Mingjiang , Zheng Guangrong , Zhou Daohong
Published: July 2020

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that utilize the ubiquitin proteasome system (UPS) to degrade proteins of interest (POI). PROTACs are potentially superior to conventional small molecule inhibitors (SMIs) because of their unique mechanism of action (MOA, i.e., degrading POI in a sub-stoichiometric manner), ability to target “undruggable” and mutant proteins, and improved target selectivity. Therefore, PROTACs have become an emerging technology for the development of novel targeted anticancer therapeutics. In fact, some of these reported PROTACs exhibit unprecedented efficacy and specificity in degrading various oncogenic proteins and have advanced to various stages of preclinical and clinical development for the treatment of cancer and hematologic malignancy. In this review, we systematically summarize the known PROTACs that have the potential to be used to treat various hematologic malignancies and discuss strategies to improve the safety of PROTACs for clinical application. Particularly, we propose to use the latest human pan-tissue single-cell RNA sequencing data to identify hematopoietic cell type-specific/selective E3 ligases to generate tumor-specific/selective PROTACs. These PROTACs have the potential to become safer therapeutics for hematologic malignancies because they can overcome some of the on-target toxicities of SMIs and PROTACs.
Expression of metalloproteinases MMP-2 and MMP-9 is associated to the presence of androgen receptor in epithelial ovarian tumors
Authors: Morales-Vásquez Flavia , Castillo-Sánchez Rocío , Gómora María J. , Almaraz Miguel Ángel , Pedernera Enrique , Pérez-Montiel Delia , Rendón Elizabeth , López-Basave Horacio Noé , Román-Basaure Edgar , Cuevas-Covarrubias Sergio , Maldonado-Cubas Juan , Villa Antonio , Mendez Carmen
Published: July 2020

Background

The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence.

Results

MMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (−) in stroma displayed a significant reduction of survival.

Conclusions

The presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.
DNA methylation repels binding of hypoxia-inducible transcription factors to maintain tumor immunotolerance
Authors: D’Anna Flora , Van Dyck Laurien , Xiong Jieyi , Zhao Hui , Berrens Rebecca V. , Qian Junbin , Bieniasz-Krzywiec Pawel , Chandra Vikas , Schoonjans Luc , Matthews Jason , De Smedt Julie , Minnoye Liesbeth , Amorim Ricardo , Khorasanizadeh Sepideh , Yu Qian , Zhao Liyun , De Borre Marie , Savvides Savvas N. , Simon M. Celeste , Carmeliet Peter , Reik Wolf , Rastinejad Fraydoon , Mazzone Massimiliano , Thienpont Bernard , Lambrechts Diether
Published: July 2020

Background

Hypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia.

Results

We report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines. Based on in silico structural modeling, we show that 5-methylcytosine indeed causes steric hindrance in the HIF binding pocket. A model wherein cell-type-specific methylation landscapes, as laid down by the differential expression and binding of other transcription factors under normoxia, control cell-type-specific hypoxia responses is observed. We also discover ectopic HIF binding sites in repeat regions which are normally methylated. Genetic and pharmacological DNA demethylation, but also cancer-associated DNA hypomethylation, expose these binding sites, inducing HIF-dependent expression of cryptic transcripts. In line with such cryptic transcripts being more prone to cause double-stranded RNA and viral mimicry, we observe low DNA methylation and high cryptic transcript expression in tumors with high immune checkpoint expression, but not in tumors with low immune checkpoint expression, where they would compromise tumor immunotolerance. In a low-immunogenic tumor model, DNA demethylation upregulates cryptic transcript expression in a HIF-dependent manner, causing immune activation and reducing tumor growth.

Conclusions

Our data elucidate the mechanism underlying cell-type-specific responses to hypoxia and suggest DNA methylation and hypoxia to underlie tumor immunotolerance.
Polymorphic mobile element insertions contribute to gene expression and alternative splicing in human tissues
Authors: Cao Xiaolong , Zhang Yeting , Payer Lindsay M. , Lords Hannah , Steranka Jared P. , Burns Kathleen H. , Xing Jinchuan
Published: July 2020

Background

Mobile elements are a major source of structural variants in the human genome, and some mobile elements can regulate gene expression and transcript splicing. However, the impact of polymorphic mobile element insertions (pMEIs) on gene expression and splicing in diverse human tissues has not been thoroughly studied. The multi-tissue gene expression and whole genome sequencing data generated by the Genotype-Tissue Expression (GTEx) project provide a great opportunity to systematically evaluate the role of pMEIs in regulating gene expression in human tissues.

Results

Using the GTEx whole genome sequencing data, we identify 20,545 high-quality pMEIs from 639 individuals. Coupling pMEI genotypes with gene expression profiles, we identify pMEI-associated expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) in 48 tissues. Using joint analyses of pMEIs and other genomic variants, pMEIs are predicted to be the potential causal variant for 3522 eQTLs and 3717 sQTLs. The pMEI-associated eQTLs and sQTLs show a high level of tissue specificity, and these pMEIs are enriched in the proximity of affected genes and in regulatory elements. Using reporter assays, we confirm that several pMEIs associated with eQTLs and sQTLs can alter gene expression levels and isoform proportions, respectively.

Conclusion

Overall, our study shows that pMEIs are associated with thousands of gene expression and splicing variations, indicating that pMEIs could have a significant role in regulating tissue-specific gene expression and transcript splicing. Detailed mechanisms for the role of pMEIs in gene regulation in different tissues will be an important direction for future studies.
Bovine breed-specific augmented reference graphs facilitate accurate sequence read mapping and unbiased variant discovery
Authors: Crysnanto Danang , Pausch Hubert
Published: July 2020

Background

The current bovine genomic reference sequence was assembled from a Hereford cow. The resulting linear assembly lacks diversity because it does not contain allelic variation, a drawback of linear references that causes reference allele bias. High nucleotide diversity and the separation of individuals by hundreds of breeds make cattle ideally suited to investigate the optimal composition of variation-aware references.

Results

We augment the bovine linear reference sequence (ARS-UCD1.2) with variants filtered for allele frequency in dairy (Brown Swiss, Holstein) and dual-purpose (Fleckvieh, Original Braunvieh) cattle breeds to construct either breed-specific or pan-genome reference graphs using the vg toolkit. We find that read mapping is more accurate to variation-aware than linear references if pre-selected variants are used to construct the genome graphs. Graphs that contain random variants do not improve read mapping over the linear reference sequence. Breed-specific augmented and pan-genome graphs enable almost similar mapping accuracy improvements over the linear reference. We construct a whole-genome graph that contains the Hereford-based reference sequence and 14 million alleles that have alternate allele frequency greater than 0.03 in the Brown Swiss cattle breed. Our novel variation-aware reference facilitates accurate read mapping and unbiased sequence variant genotyping for SNPs and Indels.

Conclusions

We develop the first variation-aware reference graph for an agricultural animal (10.5281/zenodo.3759712). Our novel reference structure improves sequence read mapping and variant genotyping over the linear reference. Our work is a first step towards the transition from linear to variation-aware reference structures in species with high genetic diversity and many sub-populations.
Illuminating the human virome in health and disease
Authors: Adiliaghdam Fatemeh , Jeffrey Kate L.
Published: July 2020

Although the microbiome is established as an important regulator of health and disease, the role of viruses that inhabit asymptomatic humans (collectively, the virome) is less defined. While we are still characterizing what constitutes a healthy or diseased virome, an exciting next step is to move beyond correlations and toward identification of specific viruses and their precise mechanisms of beneficial or harmful immunomodulation. Illuminating this will represent a first step toward developing virome-focused therapies.
Association between trust in the public healthcare system and selecting a surgeon in public hospitals in Israel: a cross-sectional population study
Authors: Niv-Yagoda Adi
Published: July 2020

Background

The Israeli public health system has seen a steady decline in public trust and confidence, which has resulted in an increased rate of individuals holding private and commercial health insurance policies that allow more choice of various services (especially choose the surgeon’s). This study evaluated the attitudes and beliefs of Israeli adults regarding public trust, equitability and choice within the public health system.

Methods

A cross-sectional telephone survey conducted among a representative random sample of Israeli adults (> 25 years). Participants responded to a 27-item questionnaire. Multivariate regression analyses were performed to determine the contribution of various socio-demographic variables to the perceptions of trust and equitability in the health system and the ability to choose a surgeon, As well as a possible links among these parameters.

Results

Of 865 adults that responded to the survey, most were women (51.8%), Jewish (68.6%), and married (73.0%). Trust in the public health system, the perception of the system’s equitability and the public’s perception of the importance of selecting a surgeon were inter-related. The results emphasize a possible association between three meaningful factors: the trust in the public health system, the perception of the system’s equitability and the public’s perception regarding the importance of selecting a surgeon.

Conclusions

Public trust in the public health system is a fundamental condition for maintaining an efficient and equitable health system in Israel. The survey suggests that uncertainty regarding the identity of the surgeon who will perform a procedure in a public hospital may be linked to a sense of insecurity and distrust of the public in the public health system. This study did not examine the causal relationship between the various factors, but the study data suggests a possible link between lower trust in the system and a lower perception of its equitability, and a subsequent associated increase in the public’s desire to select a surgeon. This study suggests to recognize public trust as a central and significant tool to strengthen public health system. One of the ways to strengthen the public’s confidence in the public health system could be to provide the patient with reliable information regarding parameters such as the identity of the senior surgeon in the operating room or the surgeon’s suitability for the patient’s medical condition.
Synergistic Effects of Polypropylene and Glass Fiber on Mechanical Properties and Durability of Recycled Aggregate Concrete
Authors: Lei Bin , Li Wengui , Liu Huajian , Tang Zhuo , Tam Vivian W. Y.
Published: July 2020

To better understand the synergistic effects of combined fibers on mechanical properties and durability of recycled aggregate concrete (RAC), different types of fibers with various lengths and mass ratios were adopted in this study. Experimental investigations were conducted to study the 28-day compressive strength and strength loss after exposed to salt-solution freeze–thaw cycles and the coupled action of mechanical loading and salt-solution freeze–thaw cycles. The microstructure was also characterized to evaluate the mechanism of this synergistic effect. To determine the effectiveness of the combined fibers on improving the mechanical properties and durability of RAC, the synergistic coefficient was proposed and applied for various combinations of fibers. The results indicate that the incorporation of fibers slightly decreased the 28-day compressive strength of RAC, but combining different sizes and types of fibers can mitigate this negative effect. Moreover, the incorporation of fibers greatly improves the freeze–thaw resistance of RAC. The combining different fibers exhibited a synergistic effect on the enhancement in properties of RAC, which could not be predicted with only one simplistic rule of fibre mixtures. In addition, microstructural characterization shows that the bonding strength of the interfacial transition zone (ITZ) between the fiber and cement matrix is mainly determined by the chemical bonding force which is due to the hydration reaction between fiber surface and cement matrix.
Controversies in acute multiligamentary knee injuries (MLKI)
Authors: Mosquera Manuel F. , Jaramillo Alejandro , Gil Ricardo , Gonzalez Yessica
Published: July 2020

Multiligament injuries of the knee (MLKI), remain an infrequent pathology especially in developed countries compared to mono-ligament lesions. In Colombia, MLKI is frequent due to the high accident rate on motorcycles. In the city of Bogota alone, about 160 motorcycle accidents have been estimated daily, being one of the cities that proportionately use this means of transport less compared to small cities. The term MLKI, include all ruptures of two or more major ligaments and therefore it has a broad spectrum of clinical presentation which creates a great challenge for the orthopedists and the surgeons envolved in this topic. The literature is rich in studies level IV but very poor in level I and level II, which generates controversies and little consensus in the diagnosis and treatment of this pathology. However there has been a gradual and better understanding of all factors involved in the treatment of MLKI that has improved the functional results of these knees in our patients, in fact we currently are more precise to achieve accurate diagnosis, evolved from not surgical approach to operate most, applying new anatomical and biomechanical concepts, with specialized and skill surgical techniques with more stable and biocompatible fixation implants, which allow in most cases to initiate an early integral rehabilitation program. Nevertheless due to the complexity and severity of the lesions, in some patients the functional results are poor. The goal of this revision is to identify the most frequent controversies in the diagnosis and treatment of MLKI, defining which of them are agreed according to what is reported in the literature and share some concepts based from the experience of more than 25 years of the senior author (MM) in the management of these injuries.

Level of Evidence

V – Expert Opinion.
Tips and tricks for building a good paper: what editors want
Authors: Karlsson Jon , Reider Bruce , Wojtys Edward M. , Zaffagnini Stefano
Published: July 2020

ESSKA is constantly committed to promoting the improvement of scientific quality through the publication of books and the organization of dedicated conferences. In line with this commitment, this interview paper was crated with the aim of being useful for all the young scientists and orthopaedics keen in musculoskeletal and sport medicine research. Three Editors from the most important journals in our field were invited to participate: Jon Karlsson from Knee Surgery Sport Traumatology and Arthroscopy, Bruce Reider from The American Journal of Sport Medicine and Edward Wojtys from Sports Health.
A development of reduction scenarios of the short-lived climate pollutants (SLCPs) for mitigating global warming and environmental problems
Authors: Nakajima Teruyuki , Ohara Toshimasa , Masui Toshihiko , Takemura Toshihiko , Yoshimura Kei , Goto Daisuke , Hanaoka Tatsuya , Itahashi Syuichi , Kurata Gakuji , Kurokawa Jun-ichi , Maki Takashi , Masutomi Yuji , Nakata Makiko , Nitta Tomoko , Seposo Xerxes , Sudo Kengo , Suzuki Chieko , Suzuki Kentaroh , Tsuruta Haruo , Ueda Kayo , Watanabe Shingo , Yu Yong , Yumimoto Keiya , Zhao Shuyun
Published: July 2020

This study presents the results of the ERTDF S-12 project for searching an optimum reduction scenario of the short-lived climate pollutants (SLCPs) to simultaneously mitigate the global warming and environmental problems. The study utilized REAS emission inventory, Asia-Pacific Integrated Model-Enduse (AIM/Enduse), MIROC6 climate model, NICAM non-hydrostatic atmospheric model, and models for estimating environmental damages to health, agriculture, and flood risks. Results of various scenario search indicate that it is difficult to attain simultaneous reduction of global warming and environmental damages, unless a significant reduction of CO2 is combined with carefully designed SLCP reductions for CH4, SO2, black carbon (BC), NOx, CO, and VOCs. In this scenario design, it is important to take into account the impact of small BC reduction to the surface air temperature and complex atmospheric chemical interactions such as negative feedback between CH4 and NOx reduction. We identified two scenarios, i.e., B2a and B1c scenarios which combine the 2D-scenario with SLCP mitigation measures using End-of-Pipe (EoP) and new mitigation technologies, as promising to simultaneously mitigate the temperature rise by about 0.33 °C by 2050 and air pollution in most of the globe for reducing damages in health, agriculture, and flood risk. In Asia and other heavy air pollution areas, health-care measures have to be enhanced in order to suppress the mortality increase due to high temperature in hot spot areas caused by a significant cut of particulate matter. For this situation, the B1b scenario is better to reduce hot spot areas and high-temperature damage to the public health.
Assessing the effect of giving and receiving written corrective feedback on improving L2 writing accuracy: does giving and receiving feedback have fair mutual benefit?
Authors: Rouhi Afsar , Dibah Minou , Mohebbi Hassan
Published: July 2020

Although the findings of second language (L2) studies conducted to date have provided evidence for the positive effect of written corrective feedback (hereafter feedback) on improving L2 learners’ writing grammatical accuracy, there is no conclusive evidence regarding which kind of feedback is more beneficial for enhancing L2 writing. This study compares the differential effects of giving and receiving unfocused direct feedback on improving Iranian EFL learners’ writing accuracy. To this end, 61 learners of English were randomly assigned to three groups, including a feedback giver group (n = 19), a feedback receiver group (n = 22), and a control group (n = 20). The participating groups took Cambridge English Preliminary Test (PET), completed four translation tasks as the treatment, and took two tests, namely a translation test and a picture description test. The data analysis indicated the effectiveness of the feedback provided by peers. Additionally, further data analysis revealed that the participants in the feedback giver group outperformed the participants in the feedback receiver and the control groups in translation and picture description tests, underscoring the positive effect of giving feedback on learners themselves rather than learners who receive feedback. The findings and potential pedagogical implications of the study are discussed in detail.
A qualitative assessment of barriers and facilitators to implementing recommended infant nutrition practices in Mumbai, India
Authors: Athavale Priyanka , Hoeft Kristin , Dalal Rupal M. , Bondre Ameya P. , Mukherjee Piyasree , Sokal-Gutierrez Karen
Published: July 2020

Background

Childhood malnutrition has been a longstanding crisis in Mumbai, India. Despite national IYCF (Infant Young Child Feeding) guidelines to promote best practices for infant/toddler feeding, nearly one-third of children under age five are stunted or underweight. To improve child nutrition, interventions should address the cultural, social, and environmental influences on infant feeding practices. This study is an in-depth qualitative assessment of family barriers and facilitators to implementing recommended nutrition practices in two Mumbai slum communities, within the context of an existing nutrition education-based intervention by a local non-governmental non-profit organization.

Methods

The population was purposively sampled to represent a variety of household demographics. Data were collected through 33 in-depth semi-structured interviews with caregivers (mothers and paternal grandmothers) of children age 0–2 years. Transcripts were translated and transcribed, and analyzed using qualitative analysis procedures and software.

Results

A complex set of barriers and facilitators influence mothers’/caregivers’ infant-toddler feeding practices. Most infants were fed complementary foods and non-nutritious processed snacks, counter to IYCF recommendations. Key barriers included: lack of nutrition knowledge and experience, receiving conflicting messages from different sources, limited social support, and poor self-efficacy for maternal decision-making. Key facilitators included: professional nutrition guidance, personal self-efficacy and empowerment, and family support. Interventions to improve child nutrition should address mothers’/caregivers’ key barriers and facilitators to recommended infant-toddler feeding practices.

Conclusions

Nutrition interventions should prioritize standard messaging across healthcare providers, engage all family members, target prevention of early introduction of sugary and non-nutritious processed foods, and strengthen maternal self-efficacy for following IYCF recommended guidelines.
Biofumigation potential of Indian mustard (Brassica juncea) to manage Rhizoctonia solani
Authors: Abdallah Ibrahim , Yehia Radwa , Kandil Mohamed Abdel-hady
Published: July 2020

In Egypt, Rhizoctonia solani is an economically important fungal pathogen on many crops such as common bean causing serious yield losses. Biofumigation with Indian mustard (Brassica juncea), as a potential alternative to the restricted fumigant methyl bromide, is gaining attention in sustainable vegetable production. In this study, laboratory and greenhouse experiments were conducted to evaluate the biofumigation effect of B. juncea, used as dry plants, seed meal, seed powder, methanol extract, and fresh plants (at the vegetative and flowering stages), against R. solani. Results showed that hexane defatted seed meal was the most efficient one, followed by the seed powder, fresh plants at the flowering stage then fresh plants at the vegetative stage. The fungal inhibition rate was 61.5, 50.2, 49.9, and 47.7%, respectively. While the dry plants at both flowering and vegetative stage recorded the lowest suppressive effect (44.3 and 39.1%, respectively). The findings open up the possibility of using the B. juncea in managing the root rot fungus, not only as a common green manure but also as a defatted seed meal.
Women in cardiology: critical status and a call to move forward
Authors: Farhan Hasan Ali , Dakhil Zainab Atiyah
Published: July 2020

Background

Healthcare workforce should mirror the population in representing patients’ diversity; however, in certain medical specialties like cardiology, there is a significant under-representation of females in fellowship programs. There is limited data discussing this issue in the Middle East, and up to our knowledge, no prior literature has cast a light on this subject in Iraq.

Main text

Women represent not a minority but rather a negligible proportion of cardiologists in the Middle East, in general, and in Iraq, in particular, as over two decades, recruiting females in cardiology training never progressed. Women are facing many challenges that explain this gender gap, mainly work–life balance and risk of exposure to radiation in addition to society’s perceptions in the Middle East that underestimate women in interventional specialties.

Conclusions

Serious efforts and forward steps should be taken by decision makers in cardiology fellowship programs and national cardiology societies to bridge this gender gap in order to improve cardiovascular care for both genders regardless of social barriers and traditional customs and to offer more access of care to those female patients who wish to be treated by female doctors based on their personal convictions.