bluuebunny/crossref_metadata_2025 huggingface dataset:
Proceedings of the biosimilars workshop at the International Symposium on Oncology Pharmacy Practice 2019
Authors: Tan Chia Jie , Ke Yu , Chan Alexandre
Published: April 2020

The International Society of Oncology Pharmacy Practitioners organized a workshop to create learning opportunities on biosimilars in pharmacy practice on 10 October 2019. The topics that were covered included (i) the development and testing of biosimilars, (ii) the challenges of bringing biosimilars to market, and (iii) real-world data on patient safety and perceptions during biosimilar implementation. The development of biosimilars can take up to eight years and the extensiveness of the process depends on several factors, such as the complexity of the production process and regulatory requirements. Compared to generic products of small-molecule drugs, there is a higher barrier to market entry for biosimilars, explaining the small number of biosimilars in the market. Appraisal of biosimilars for inclusion in hospital formularies is also different from the review process of originator biologics, where the former is usually institution-led and has fewer restrictions on use. When several biosimilar products are available, factors that should be considered besides cost are licensed indications, supply chain confidence, clinical data, and product attributes. Real-world data have shown that biosimilars are well-tolerated and have safety data that are comparable to that of the originator product. Oncology pharmacists from the United Kingdom, Kenya, and Canada also presented their respective experiences with biosimilar use. Different countries at varying stages of biosimilar implementation faced distinct challenges. Nevertheless, resources to assist biosimilar implementation can potentially be shared between different regions. International Society of Oncology Pharmacy Practitioners is well-positioned to foster professional cooperation at an international level to drive biosimilar implementation.
Measure for Measure: Measuring the Usefulness of Measuring Antiseizure Medication Levels
Authors: Faught Edward
Published: April 2020

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Resection of Internal Carotid Artery Aneurysm Under Neuroprotection With Flow Reversal Technique
Authors: Mukherjee Dipankar , Collins Devon T. , Adams Laura
Published: April 2020

Extracranial internal carotid artery (ICA) aneurysms account for <1.0% all aneurysms and a rare indication for carotid intervention. Causes include atherosclerotic degeneration, trauma, dissection, previous carotid surgery, connective tissue disorders, and infection. Authors report a case of a middle-aged male found to have a large aneurysm of the left ICA who underwent repair by resection and reconstruction with end-to-end anastomosis under neuroprotection with flow reversal. Our discussion includes a recommendation for this particular surgical repair. The patient in this case report has granted the authors consent for review of records and subsequent publication submission.
Long-Term Outcome of Chimney Technique Using a Balloon-Expandable Bare-Metal Stent to Preserve Supra-Arch Branches in Type B Aortic Dissection
Authors: Sun Guoyi , Ge Yang-yang , Guo Wei , Jia Xin , Rong Dan , Liu Xiao-ping , Xiong Jiang , Zhang Hong-peng , Ma Xiao-hui
Published: April 2020

Purpose:

This study was performed to investigate the long-term effect of chimney technique using balloon-expandable bare-metal stents (BMSs) to preserve the supra-arch branches in type B aortic dissection (TBAD).

Methods:

Fifty patients with TBAD treated by thoracic endovascular aortic repair with the chimney technique (chTEVAR) using balloon-expandable BMSs from July 2009 to December 2013 were retrospectively assessed. Follow-up computed tomography angiography was performed to assess the postoperative outcomes. The primary end point was a persistent type Ia endoleak (ELIa). The secondary endpoints were chimney stent (CS)-based complications (stenosis, occlusion, fracture, or transposition), all-cause mortality, reintervention, and stroke.

Results:

Fifty supra-arch branches (left common carotid artery, n = 11; left subclavian artery, n = 39) were preserved via the chimney technique with 50 balloon-expandable BMSs. The technical success rate was 100%. An immediate ELIa was discovered in 9 (18%) patients. The median survival duration during follow-up was 77.3 months. Five (10%) patients had a persistent ELIa; 3 of these patients had an immediate ELIa. Asymptomatic CS-based complications were found in 3 (6%) patients. The all-cause mortality rate was 8% (4/50); 2 deaths were aortic-related deaths. Five (10%) patients underwent a reintervention. During the estimated 36-month survival period, the survival rate, the rate of freedom from persistent ELIa, and the rate of freedom from reintervention were 93.87%, 89.48%, and 95.56%, respectively.

Conclusions:

The long-term outcomes showed that chTEVAR using balloon-expandable BMSs was safe and feasible for preservation of the supra-arch branches. Evaluation of more patients with a longer follow-up period is needed.
Opioid Use After Common Sports Medicine Procedures: A Systematic Review
Authors: Sheth Ujash , Mehta Mitesh , Huyke Fernando , Terry Michael A. , Tjong Vehniah K.
Published: April 2020

Context:

The prescription of opioids after elective surgical procedures has been a contributing factor to the current opioid epidemic in North America.

Objective:

To examine the opioid prescribing practices and rates of opioid consumption among patients undergoing common sports medicine procedures.

Data Sources:

A systematic review of the electronic databases EMBASE, MEDLINE, and PubMed was performed from database inception to December 2018.

Study Selection:

Two investigators independently identified all studies reporting on postoperative opioid prescribing practices and consumption after arthroscopic shoulder, knee, or hip surgery. A total of 119 studies were reviewed, with 8 meeting eligibility criteria.

Study Design:

Systematic review.

Level of Evidence:

Level 4.

Data Extraction:

The quantity of opioids prescribed and used were converted to milligram morphine equivalents (MMEs) for standardized reporting. The quality of each eligible study was evaluated using the Methodological Index for Non-Randomized Studies.

Results:

A total of 8 studies including 816 patients with a mean age of 43.8 years were eligible for inclusion. A mean of 610, 197, and 613 MMEs were prescribed to patients after arthroscopic procedures of the shoulder, knee, and hip, respectively. At final follow-up, 31%, 34%, and 64% of the prescribed opioids provided after shoulder, knee, and hip arthroscopy, respectively, still remained. The majority of patients (64%) were unaware of the appropriate disposal methods for surplus medication. Patients undergoing arthroscopic rotator cuff repair had the highest opioid consumption (471 MMEs), with 1 in 4 patients receiving a refill.

Conclusion:

Opioids are being overprescribed for arthroscopic procedures of the shoulder, knee, and hip, with more than one-third of prescribed opioids remaining postoperatively. The majority of patients are unaware of the appropriate disposal techniques for surplus opioids. Appropriate risk stratification tools and evidence-based recommendations regarding pain management strategies after arthroscopic procedures are needed to help curb the growing opioid crisis.
Segmental Mandibular Reconstruction Using Tissue Engineering Strategies: A Systematic Review of Individual Patient Data
Authors: Kumar Vinay V. , Rometsch Elke , Thor Andreas , Wolvius Eppo , Hurtado-Chong Anahí
Published: April 2020

Objective:

The aim of the systematic review was to analyze the current clinical evidence concerning the use of tissue engineering as a treatment strategy for reconstruction of segmental defects of the mandible and their clinical outcomes using individual patient data.

Methods:

A systematic review of the literature was conducted using PubMed and Cochrane Library on May 21, 2019. The eligibility criteria included patients in whom segmental mandibular reconstruction was carried out using tissue engineering as the primary treatment strategy. After screening and checking for eligibility, individual patient data were extracted to the extent it was available. Data extraction included the type of tissue engineering strategy, demographics, and indication for treatment, and outcomes included clinical and radiographic outcome measures, vitality of engineered bone, dental rehabilitation, and patient-reported outcome measures and complications.

Results:

Out of a total of 408 articles identified, 44 articles reporting on 285 patients were included, of which 179 patients fulfilled the inclusion criteria. The different tissue engineering treatment strategies could be broadly classified into 5 groups: “prefabrication,” “cell culture,” “bone morphogenetic protein (BMP) without autografts,” “BMP with autografts,” and “scaffolds containing autografts.” Most included studies were case reports or case series. A wide variety of components were used as scaffolds, cells, and biological substances. There was not a single outcome measure that was both objective and consistently reported, although most studies reported successful outcome.

Discussion:

A wide variety of tissue engineering strategies were used for segmental mandibular reconstruction that could be classified into 5 groups. Due to the low number of treated patients, lack of standardized and consistent reporting outcomes, lack of comparative studies, and low evidence of reported literature, there is insufficient evidence to recommend any particular tissue engineering strategy.
“Treat and repair” strategy for shunt lesions: a critical review
Authors: Arvind Balaji , Relan Jay , Kothari Shyam S.
Published: April 2020

The issue of operability in patients with shunt lesions and raised pulmonary vascular resistance is contentious. Several reports suggest that patients traditionally considered inoperable may be operated after treatment with targeted drug therapy for pulmonary arterial hypertension. We reviewed all the published literature of “treat and repair” approach to gain more insights into the utility of this approach. A critical appraisal of the published literature suggests that this approach is less established for patients with post tricuspid shunts, and for patients with pre‐tricuspid shunts with modestly elevated indexed pulmonary vascular resistance (possibly greater than 11 WU.m2). Targeted drug therapy may be able to extend the therapeutic window in carefully selected patients, but its use as a routine in this setting seems unwarranted.
Genomic and molecular alterations in human inflammatory bowel disease‐associated colorectal cancer
Authors: Muller Marie , Hansmannel Franck , Arnone Djesia , Choukour Myriam , Ndiaye Ndeye Coumba , Kokten Tunay , Houlgatte Rémi , Peyrin‐Biroulet Laurent
Published: April 2020

Patients with inflammatory bowel disease are at increased risk of colorectal cancer, which has worse prognosis than sporadic colorectal cancer. Until recently, understanding of pathogenesis in inflammatory bowel disease‐associated colorectal cancer was restricted to the demonstration of chromosomic/microsatellite instabilities and aneuploidy. The advance of high‐throughput sequencing technologies has highlighted the complexity of the pathobiology and revealed recurrently mutated genes involved in the RTK/RAS, PI3K, WNT, and TGFβ pathways, leading to potentially new targetable mutations. Moreover, alterations of mitochondrial DNA and the dysregulation of non‐coding sequences have also been described, as well as several epigenetic modifications. Although recent studies have brought new insights into pathobiology and raised the prospect of innovative therapeutic approaches, the understanding of colorectal carcinogenesis in inflammatory bowel disease and how it differs from sporadic colorectal cancer remains not fully elucidated. Further studies are required to better understand the pathogenesis and molecular alterations leading to human inflammatory bowel disease‐associated colorectal cancer.
Bridging the Unbridged: A Case Study of a U.S. University’s Study Abroad Program in Beijing
Authors: Wang Yong , Li Ke , Zhang Yuan
Published: April 2020

Purpose:

Studying abroad is an important way for universities to cultivate talent with international vision and global competitiveness. Based on its analysis of a U.S. university’s study in China program, this study provides policy recommendations to promote the overseas study and exchange of U.S. students in China.

Design/Approach/Methods:

This study examines the Beijing Overseas Learning Program of L University to examine the actual operations of a study abroad program in China. More specifically, this study examines the cooperative institution where the U.S. study program is located in China to analyze the operation mechanism and underlying logical framework of the program.

Findings:

This study provides a comprehensive analysis of the logical factors as well as internal and external reasons behind U.S. students’ decisions to study in China. This study demonstrates that the “peer factor” has a decisive influence on students’ decisions to study in China.

Originality/Value:

Study abroad programs constitute an integral part of China’s initiatives to enhance people-to-people exchanges with other countries. This study improves our understanding of the practical dynamics of study abroad programs in China, thereby enhancing abilities to attract U.S. students to study in China.
Is There a Role for CT Pan-Scans in the Initial Workup of Fragility Fracture Patients?
Authors: Lepkowsky Eric , Simcox Trevor , Rogoff Hunter , Barzideh Omid , Islam Shahidul
Published: April 2020

Introduction:

Computed tomography (CT) pan-scans have become increasingly commonplace as part of the initial diagnostic workup for patients sustaining traumatic injuries. They have proven effective in improving diagnostic accuracy in those with high-energy mechanisms of injury. However, the utility of pan-scans in the geriatric population sustaining low-energy traumatic injuries remains unproven.

Methods:

A retrospective review was conducted of patients who sustained a fragility fracture at a level-1 trauma center over a 15-month period. Radiologist interpretations of any CT pan-scans were reviewed for acute findings, and charts were reviewed for resulting changes in orthopedic and nonorthopedic management. Additionally, mechanism of injury, definitive management, time to surgery, length of stay, level of care at discharge, and demographic data were compared against similar patients who did not receive a pan-scan.

Results:

Of the 109 patients who underwent a CT pan-scan, 1 (0.92%) had a change in orthopedic treatment. Twelve (11.01%) patients had changes to their nonorthopedic management. In addition, 14 other patients had one or more consultations obtained based on pan-scan results that did not result in any change in management.

Discussion:

This study found that only 1 of the included patients had a change in orthopedic management and 12 had a change in nonorthopedic management, despite over half of the study population being found to have additional findings. Furthermore, patients who underwent a pan-scan did not have expedited surgical intervention or earlier discharges compared to those who were not pan-scanned.  

Conclusion:

This study demonstrates whole-body CT imaging provides little benefit in geriatric patients who sustain fragility fractures and should be utilized judiciously and in a targeted fashion instead of as a routine part of trauma surgery or emergency department protocol in this patient population.

Level of Evidence:

Level III Retrospective Study.
Evaluation of the Influence of Head Movement on Hearing Aid Algorithm Performance Using Acoustic Simulations
Authors: Hendrikse Maartje M. E. , Grimm Giso , Hohmann Volker
Published: April 2020

Head movements can improve sound localization performance and speech intelligibility in acoustic environments with spatially distributed sources. However, they can affect the performance of hearing aid algorithms, when adaptive algorithms have to adjust to changes in the acoustic scene caused by head movement (the so-called maladaptation effect) or when directional algorithms are not facing in the optimal direction because the head has moved away (the so-called misalignment effect). In this article, we investigated the mechanisms behind these maladaptation and misalignment effects for a set of six standard hearing aid algorithms using acoustic simulations based on premade databases; this was done so we could study the effects as carefully as possible. Experiment 1 investigated the maladaptation effect by analyzing hearing aid benefit after simulated rotational head movement in simple anechoic noise scenarios. The effects of movement parameters (start angle and peak velocity), noise scenario complexity, and adaptation time were studied, as well as the recovery time of the algorithms. However, a significant maladaptation effect was only found in the most unrealistic anechoic scenario with one noise source. Experiment 2 investigated the effects of maladaptation and misalignment using previously recorded natural head movements in acoustic scenes resembling everyday life situations. In line with the results of Experiment 1, no effect of maladaptation was found in these more realistic acoustic scenes. However, a significant effect of misalignment on the performance of directional algorithms was found. This demonstrates the need to take head movement into account in the evaluation of directional hearing aid algorithms.
Mechanistic basis and efficacy of targeting the β-catenin–TCF7L2–JMJD6–c-Myc axis to overcome resistance to BET inhibitors
Authors: Saenz Dyana T. , Fiskus Warren , Mill Christopher P. , Perera Dimuthu , Manshouri Taghi , Lara Bernardo H. , Karkhanis Vrajesh , Sharma Sunil , Horrigan Stephen K. , Bose Prithviraj , Kadia Tapan M. , Masarova Lucia , DiNardo Courtney D. , Borthakur Gautam , Khoury Joseph D. , Takahashi Koichi , Bhaskara Srividya , Lin Charles Y. , Green Michael R. , Coarfa Cristian , Crews Craig M. , Verstovsek Srdan , Bhalla Kapil N.
Published: April 2020

The promising activity of BET protein inhibitors (BETi’s) is compromised by adaptive or innate resistance in acute myeloid leukemia (AML). Here, modeling of BETi-persister/resistance (BETi-P/R) in human postmyeloproliferative neoplasm (post-MPN) secondary AML (sAML) cells demonstrated accessible and active chromatin in specific superenhancers/enhancers, which was associated with increased levels of nuclear β-catenin, TCF7L2, JMJD6, and c-Myc in BETi-P/R sAML cells. Following BETi treatment, c-Myc levels were rapidly restored in BETi-P/R sAML cells. CRISPR/Cas9-mediated knockout of TCF7L2 or JMJD6 reversed BETi-P/R, whereas ectopic overexpression conferred BETi-P/R in sAML cells, confirming the mechanistic role of the β-catenin–TCF7L2–JMJD6–c-Myc axis in BETi resistance. Patient-derived, post-MPN, CD34+ sAML blasts exhibiting relative resistance to BETi, as compared with sensitive sAML blasts, displayed higher messenger RNA and protein expression of TCF7L2, JMJD6, and c-Myc and following BETi washout exhibited rapid restoration of c-Myc and JMJD6. CRISPR/Cas9 knockout of TCF7L2 and JMJD6 depleted their levels, inducing loss of viability of the sAML blasts. Disruption of colocalization of nuclear β-catenin with TBL1 and TCF7L2 by the small-molecule inhibitor BC2059 combined with depletion of BRD4 by BET proteolysis-targeting chimera reduced c-Myc levels and exerted synergistic lethality in BETi-P/R sAML cells. This combination also reduced leukemia burden and improved survival of mice engrafted with BETi-P/R sAML cells or patient-derived AML blasts innately resistant to BETi. Therefore, multitargeted disruption of the β-catenin–TCF7L2–JMJD6–c-Myc axis overcomes adaptive and innate BETi resistance, exhibiting preclinical efficacy against human post-MPN sAML cells.
Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line
Authors: Mengozzi Manuela , Hesketh Andrew , Bucca Giselda , Ghezzi Pietro , Smith Colin P.
Published: April 2020

Background

Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation.

Methods

Gene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction top-values, and significant genes were grouped into co-expression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package.

Results

Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway.

Conclusions

This study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.
Long non-coding RNA H19, a novel therapeutic target for pancreatic cancer
Authors: Wang Jing , Zhao Lei , Shang Kun , Liu Fang , Che Juanjuan , Li Huihui , Cao Bangwei
Published: April 2020

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, which threats peoples’ health. Unfortunately, the pathogenesis of PDAC remains unclear. Recent studies have indicated that long non-coding RNAs (lncRNAs) can regulate the development and progression of malignant tumors through varying mechanisms. LncRNA H19 has a unique expression profile and can act as a sponger of specific miRNAs to regulate the pathogenic process of many diseases, including PDAC and several other types of cancers. Here, we review the research approaches to understanding the regulatory role of H19 and potential mechanisms in the progression of PDAC and other types of cancers and diseases. These studies suggest that H19 may be a novel therapeutic target for PDAC and our findings may open new revenues for scientific researches and development of valuable therapies for these diseases in the future.
2D/2D Heterojunction of R-scheme Ti3C2 MXene/MoS2 Nanosheets for Enhanced Photocatalytic Performance
Authors: Yao Ziyu , Sun Huajun , Sui Huiting , Liu Xiaofang
Published: April 2020

Combination of two-dimensional (2D) materials and semiconductors is considered to be an effective way for fabricating photocatalysts for solving the environmental pollution and energy crisis. In this work, novel 2D/2D heterojunction of R-scheme Ti3C2 MXene/MoS2 nanosheets is successfully synthesized by hydrothermal reaction. The photocatalytic activity of the Ti3C2 MXene/MoS2 composites is evaluated by photocatalytic degradation and hydrogen evolution reaction. Especially, 0.5 wt% Ti3C2 MXene/MoS2 sample exhibits optimum methyl orange (MO) degradation and H2 evolution rate of 97.4% and H2 evolution rate of 380.2 μmol h−1 g−1, respectively, which is attributed to the enhanced optical absorption ability and increased specific surface area. Additionally, Ti3C2 MXene coupled with MoS2 nanosheets is favorable for improving the photocurrent response and reducing the electrochemical impedance, leading to the enhanced electron transfer of excited semiconductor and inhibition of charge recombination. This work demonstrates that Ti3C2 MXene could be a promising carrier to construct 2D/2D heterojunction in photocatalytic degradation and hydrogen evolution reaction.
Toxo: a library for calculating penetrance tables of high-order epistasis models
Authors: Ponte-Fernández Christian , González-Domínguez Jorge , Carvajal-Rodríguez Antonio , Martín María J.
Published: April 2020

Background

Epistasis is defined as the interaction between different genes when expressing a specific phenotype. The most common way to characterize an epistatic relationship is using a penetrance table, which contains the probability of expressing the phenotype under study given a particular allele combination. Available simulators can only create penetrance tables for well-known epistasis models involving a small number of genes and under a large number of limitations.

Results

Toxo is a MATLAB library designed to calculate penetrance tables of epistasis models of any interaction order which resemble real data more closely. The user specifies the desired heritability (or prevalence) and the program maximizes the table’s prevalence (or heritability) according to the input epistatic model boundaries.

Conclusions

Toxo extends the capabilities of existing simulators that define epistasis using penetrance tables. These tables can be directly used as input for software simulators such as GAMETES so that they are able to generate data samples with larger interactions and more realistic prevalences/heritabilities.
Investigation of sequence features of hinge-bending regions in proteins with domain movements using kernel logistic regression
Authors: Veevers Ruth , Cawley Gavin , Hayward Steven
Published: April 2020

Background

Hinge-bending movements in proteins comprising two or more domains form a large class of functional movements. Hinge-bending regions demarcate protein domains and collectively control the domain movement. Consequently, the ability to recognise sequence features of hinge-bending regions and to be able to predict them from sequence alone would benefit various areas of protein research. For example, an understanding of how the sequence features of these regions relate to dynamic properties in multi-domain proteins would aid in the rational design of linkers in therapeutic fusion proteins.

Results

The DynDom database of protein domain movements comprises sequences annotated to indicate whether the amino acid residue is located within a hinge-bending region or within an intradomain region. Using statistical methods and Kernel Logistic Regression (KLR) models, this data was used to determine sequence features that favour or disfavour hinge-bending regions. This is a difficult classification problem as the number of negative cases (intradomain residues) is much larger than the number of positive cases (hinge residues). The statistical methods and the KLR models both show that cysteine has the lowest propensity for hinge-bending regions and proline has the highest, even though it is the most rigid amino acid. As hinge-bending regions have been previously shown to occur frequently at the terminal regions of the secondary structures, the propensity for proline at these regions is likely due to its tendency to break secondary structures. The KLR models also indicate that isoleucine may act as a domain-capping residue. We have found that a quadratic KLR model outperforms a linear KLR model and that improvement in performance occurs up to very long window lengths (eighty residues) indicating long-range correlations.

Conclusion

In contrast to the only other approach that focused solely on interdomain hinge-bending regions, the method provides a modest and statistically significant improvement over a random classifier. An explanation of the KLR results is that in the prediction of hinge-bending regions a long-range correlation is at play between a small number amino acids that either favour or disfavour hinge-bending regions. The resulting sequence-based prediction tool, HingeSeek, is available to run through a webserver at hingeseek.cmp.uea.ac.uk.
A benchmark study of ab initio gene prediction methods in diverse eukaryotic organisms
Authors: Scalzitti Nicolas , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie D.
Published: April 2020

Background

The draft genome assemblies produced by new sequencing technologies present important challenges for automatic gene prediction pipelines, leading to less accurate gene models. New benchmark methods are needed to evaluate the accuracy of gene prediction methods in the face of incomplete genome assemblies, low genome coverage and quality, complex gene structures, or a lack of suitable sequences for evidence-based annotations.

Results

We describe the construction of a new benchmark, called G3PO (benchmark for Gene and Protein Prediction PrOgrams), designed to represent many of the typical challenges faced by current genome annotation projects. The benchmark is based on a carefully validated and curated set of real eukaryotic genes from 147 phylogenetically disperse organisms, and a number of test sets are defined to evaluate the effects of different features, including genome sequence quality, gene structure complexity, protein length, etc. We used the benchmark to perform an independent comparative analysis of the most widely used ab initio gene prediction programs and identified the main strengths and weaknesses of the programs. More importantly, we highlight a number of features that could be exploited in order to improve the accuracy of current prediction tools.

Conclusions

The experiments showed that ab initio gene structure prediction is a very challenging task, which should be further investigated. We believe that the baseline results associated with the complex gene test sets in G3PO provide useful guidelines for future studies.
Genetic and phenotypic associations between root architecture, arbuscular mycorrhizal fungi colonisation and low phosphate tolerance in strawberry (Fragaria × ananassa)
Authors: Cockerton Helen Maria , Li Bo , Stavridou Eleftheria , Johnson Abigail , Karlström Amanda , Armitage Andrew Douglas , Martinez-Crucis Ana , Galiano-Arjona Lorena , Harrison Nicola , Barber-Pérez Nuria , Cobo-Medina Magdalena , Harrison Richard Jonathan
Published: April 2020

Background

Phosphate is an essential plant macronutrient required to achieve maximum crop yield. Roots are able to uptake soil phosphate from the immediate root area, thus creating a nutrient depletion zone. Many plants are able to exploit phosphate from beyond this root nutrient depletion zone through symbiotic association with Arbuscular Mycorrhizal Fungi (AMF). Here we characterise the relationship between root architecture, AMF association and low phosphate tolerance in strawberries. The contrasting root architecture in the parental strawberry cultivars ‘Redgauntlet’ and ‘Hapil’ was studied through a mapping population of 168 progeny. Low phosphate tolerance and AMF association was quantified for each genotype to allow assessment of the phenotypic and genotypic relationships between traits.

Results

A “phosphate scavenging” root phenotype where individuals exhibit a high proportion of surface lateral roots was associated with a reduction in root system size across genotypes. A genetic correlation between “root system size” traits was observed with a network of pleiotropic QTL found to represent five “root system size” traits. By contrast, average root diameter and the distribution of roots appeared to be under two discrete methods of genetic control. A total of 18 QTL were associated with plant traits, 4 of which were associated with solidity that explained 46% of the observed variation. Investigations into the relationship between AMF association and root architecture found that a higher root density was associated with greater AMF colonisation across genotypes. However, no phenotypic correlation or genotypic association was found between low phosphate tolerance and the propensity for AMF association, nor root architectural traits when plants are grown under optimal nutrient conditions.

Conclusions

Understanding the genetic relationships underpinning phosphate capture can inform the breeding of strawberry varieties with better nutrient use efficiency. Solid root systems were associated with greater AMF colonisation. However, low P-tolerance was not phenotypically or genotypically associated with root architecture traits in strawberry plants. Furthermore, a trade-off was observed between root system size and root architecture type, highlighting the energetic costs associated with a “phosphate scavenging” root architecture.
Ovarian metastases from ileum cancer in a patient with germline EPCAM gene deletion successfully treated with surgical resection and CAPOX chemotherapy: a case report
Authors: Iwata Narushi , Shikama Ayumi , Takao Wataru , Hosokawa Yoshihiko , Itagaki Hiroya , Tasaka Nobutaka , Akiyama Azusa , Ochi Hiroyuki , Minaguchi Takeo , Arita Miwa , Noguchi Emiko , Moriwaki Toshikazu , Satoh Toyomi
Published: April 2020

Background

Despite recent findings that epithelial cell adhesion molecule (EPCAM) deletions can cause Lynch syndrome (LS), its clinical characteristics are still unknown. We present the first case of ileum cancer in a patient with germline EPCAM gene deletion, which was discovered during ovarian tumor surgery.

Case presentation

A 59-year-old woman presented with a history of colon cancer occurring at 38 and 55 years old. Five of her siblings had a history of colon cancer, and an elder sister had confirmed LS. As imaging examination revealed an ovarian tumor, and we performed hysterectomy and bilateral salpingo-oophorectomy. Careful observation during surgery revealed a cherry-sized tumor in the ileum, prompting partial ileal resection. Pathological examination showed the ovarian tumor to be a metastasis of ileum cancer. Genetic testing with blood-relative information using multiplex ligation-dependent probe amplification showed EPCAM exons 8 and 9 deletions, confirming LS. The patient received adjuvant chemotherapy with CAPOX (capecitabine and oxaliplatin) and has remained disease-free for 24 months.

Conclusions

We were fortunate to identify ileum cancer that would have been difficult to find preoperatively through careful observation during ovarian tumor surgery and successfully treated the patient by using surgical resection and CAPOX chemotherapy. When treating patients with hereditary cancer syndromes including LS, we should keep all associated cancers in mind.
Preeclampsia management modalities and perinatal death: a retrospective study in Woldia general hospital
Authors: Tlaye Kenean Getaneh , Endalfer Melese Linger , Kassaw Mesfin Wudu , Gebremedhin Mussie Mulugeta , Aynalem Yared Asmare
Published: April 2020

Background

Hypertensive disorders of pregnancy are among the most common causes of perinatal death. The disorders are highly linked to multiple factors that make prediction and prevention challenging. Early diagnosis and proper management play a crucial role in the wellbeing and life of the women and her baby. In this study, we aimed to assess the association between different management options of preeclampsia and perinatal death at a public hospital in Ethiopia.

Methods

A document review was conducted on 241 preeclamptic patients’ medical files who have been admitted and delivered in Woldia General Hospital from 2011 to 2016. The study was conducted from August 8 – September 10, 2017 in the aforementioned public hospital in Woldia town, Ethiopia. Associations were tested using Pearson chi squared test and binary logistic regression with a p-value < 0.05 considered significant.

Result

In this study, nearly 20 every 100 neonates from preeclamptic women has been died and the figure was higher (76.59% Vs 23.4%) among neonates from severe preeclamptic women than mild preeclamptic women (p = 0.01). More than two thirds of the patients (69.3%) received magnesium sulfate to prevent convulsion. Perinatal death among women with diastolic blood pressures greater than 110 mmHg at admission was nearly 3 times (Adjusted Odds Ratio (AOR) = 2.824; 95% Confidence Interval (CI) (1.154–6.038)) higher compared to women with diastolic blood pressures below 110 mmHg.

Conclusion

In the 5-year period, the magnitude of perinatal death among inpatient preeclamptic women was remarkably high and of which stillbirths exceeded pre-discharge early neonatal death. Utilization of magnesium sulfate tended to increase across years. Maternal diastolic blood pressure at admission was significantly associated with perinatal death.
Screening differentially expressed genes of pancreatic cancer between Mongolian and Han people using bioinformatics technology
Authors: Xu Jiasheng , Liao Kaili , Fu Zhonghua , Xiong Zhenfang
Published: April 2020

Background

To screen and analyze differentially expressed genes in pancreatic carcinoma tissues taken from Mongolian and Han patients by Affymetrix Genechip. Methods: Pancreatic ductal cell carcinoma tissues were collected from the Mongolian and Han patients undergoing resection in the Second Affiliated Hospital of Nanchang University from March 2015 to May 2018 and the total RNA was extracted. Differentially expressed genes were selected from the total RNA qualified by Nanodrop 2000 and Agilent 2100 using Affymetrix and a cartogram was drawn; The gene ontology (GO) analysis and Pathway analysis were used for the collection and analysis of biological information of these differentially expressed genes. Finally, some differentially expressed genes were verified by real-time PCR.

Results

Through the microarray analysis of gene expression, 970 differentially expressed genes were detected by comparing pancreatic cancer tissue samples between Mongolian and Han patients. A total of 257 genes were significantly up-regulated in pancreatic cancer tissue samples in Mongolian patients; while a total of 713 genes were down-regulated. In the Gene Ontology database, 815 differentially expressed genes were identified with clear GO classification, and CPB1 gene showed the highest increase in expression level (multiple difference: 31.76). The pathway analysis detected 28 signaling pathways that included these differentially expressed genes, involving a total of 178 genes. Among these pathways, the enrichment of differentially expressed genes in the FAK signaling pathway was the strongest and COL11A1 gene showed the highest multiple difference (multiple difference: 5.02). The expression of differentially expressed genes CPB1, COL11A1、ITGA4、BIRC3、PAK4、CPA1、CLPS、PIK3CG and HLA-DPA1 determined by real-time PCR were consistent with the results of gene microarray analysis.

Conclusions

The results of microarray analysis of gene expression profiles showed that there are a large number of differentially expressed genes in pancreatic cancer tissue samples comparing Mongolian and Han population. These genes are closely related to the cell proliferation, differentiation, invasion, metastasis and multi-drug resistance in pancreatic cancer. They are also involved in the regulation of multiple important signaling pathways in organisms.
Mediating role of coping style on the relationship between job stress and subjective well-being among Korean police officers
Authors: Ryu Gi Wook , Yang Yong Sook , Choi Mona
Published: April 2020

Background

Police officers have long been known to have one of the most stressful occupations. This study investigates their stress levels, coping styles, and subjective well-being, including affect and life satisfaction. We also explore the interrelationships of these factors to determine how coping style influences a police officer’s subjective well-being.

Methods

We used a convenience sampling method for 112 police officers in a metropolitan area in South Korea. Data were collected using self-administered questionnaires. The questionnaires consisted of the following scales: job stress, coping style, positive/negative affect, and life satisfaction that measured subjective well-being. Descriptive statistics,a correlation analysis and Hayes’ PROCESS macro, and bootstrap analysis were performed.

Results

The level of job stress for the participants was moderate, with an average of 43.57 out of 100. The mean scores of positive affect was 17.38 out of 40, 8.50 out of 40 for negative affect, and 20.76 out of 35 for life satisfaction. Job stress and coping were significantly correlated with subjective well-being, and problem-solving style mediated stress, positive affect, and life satisfaction. Lastly, assistance pursuit style mediated stress and positive affect.

Conclusions

Participants’ problem-solving and assistance pursuit coping styles were shown as important mediating factors for stress and subjective well-being, especially positive affect. These findings need to be considered when planning interventions and implementing strategies focusing on the psychosocial health of the improvement of police officers’ well-being.
Insights into the origin of metazoan multicellularity from predatory unicellular relatives of animals
Authors: Tikhonenkov Denis V. , Hehenberger Elisabeth , Esaulov Anton S. , Belyakova Olga I. , Mazei Yuri A. , Mylnikov Alexander P. , Keeling Patrick J.
Published: April 2020

Background

The origin of animals from their unicellular ancestor was one of the most important events in evolutionary history, but the nature and the order of events leading up to the emergence of multicellular animals are still highly uncertain. The diversity and biology of unicellular relatives of animals have strongly informed our understanding of the transition from single-celled organisms to the multicellular Metazoa. Here, we analyze the cellular structures and complex life cycles of the novel unicellular holozoansPigoraptorandSyssomonas(Opisthokonta), and their implications for the origin of animals.

Results

SyssomonasandPigoraptorare characterized by complex life cycles with a variety of cell types including flagellates, amoeboflagellates, amoeboid non-flagellar cells, and spherical cysts. The life cycles also include the formation of multicellular aggregations and syncytium-like structures, and an unusual diet for single-celled opisthokonts (partial cell fusion and joint sucking of a large eukaryotic prey), all of which provide new insights into the origin of multicellularity in Metazoa. Several existing models explaining the origin of multicellular animals have been put forward, but these data are interestingly consistent with one, the “synzoospore hypothesis.”

Conclusions

The feeding modes of the ancestral metazoan may have been more complex than previously thought, including not only bacterial prey, but also larger eukaryotic cells and organic structures. The ability to feed on large eukaryotic prey could have been a powerful trigger in the formation and development of both aggregative (e.g., joint feeding, which also implies signaling) and clonal (e.g., hypertrophic growth followed by palintomy) multicellular stages that played important roles in the emergence of multicellular animals.
Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor
Authors: Zhang Deling , Liu Hua , Zhang Yemin , Li Junfeng , Fu Yalin , Zheng Yuyang , Wu Jie , Ma Mingke , Wen Zhongyuan , Wang Changhua
Published: April 2020

Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action.
The endless frontier? The recent increase of R&D productivity in pharmaceuticals
Authors: Pammolli Fabio , Righetto Lorenzo , Abrignani Sergio , Pani Luca , Pelicci Pier Giuseppe , Rabosio Emanuele
Published: April 2020

Background

Studies on the early 2000s documented increasing attrition rates and duration of clinical trials, leading to a representation of a “productivity crisis” in pharmaceutical research and development (R&D). In this paper, we produce a new set of analyses for the last decade and report a recent increase of R&D productivity within the industry.

Methods

We use an extensive data set on the development history of more than 50,000 projects between 1990 and 2017, which we integrate with data on sales, patents, and anagraphical information on each institution involved. We devise an indicator to quantify the novelty of each project, based on its set of mechanisms of action.

Results

First, we investigate how R&D projects are allocated across therapeutic areas and find a polarization towards high uncertainty/high potential reward indications, with a strong focus on oncology. Second, we find that attrition rates have been decreasing at all stages of clinical research in recent years. In parallel, for each phase, we observe a significant reduction of time required to identify projects to be discontinued. Moreover, our analysis shows that more recent successful R&D projects are increasingly based on novel mechanisms of action and target novel indications, which are characterized by relatively small patient populations. Third, we find that the number of R&D projects on advanced therapies is also growing. Finally, we investigate the relative contribution to productivity variations of different types of institutions along the drug development process, with a specific focus on the distinction between the roles of Originators and Developers of R&D projects. We document that in the last decade Originator–Developer collaborations in which biotech companies act as Developers have been growing in importance. Moreover, we show that biotechnology companies have reached levels of productivity in project development that are equivalent to those of large pharmaceutical companies.

Conclusions

Our study reports on the state of R&D productivity in the bio-pharmaceutical industry, finding several signals of an improving performance, with R&D projects becoming more targeted and novel in terms of indications and mechanisms of action.