bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients
Authors: Ibrahim Iman H , Abdel-Aziz Heba G , Hassan Fatema EM , El-Sameea Hesham SA
Published: September 2020

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism.

Impact statement

GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.
Hashimoto’s Encephalopathy Revealed by Hypochondriacal Delusion: A Case Report Involving a Male Patient
Authors: Amamou Badii , Ben Saida Imen , Ben Haouala Amjed , Mhalla Ahmed , Zaafrane Ferid , Gaha Lotfi
Published: September 2020

Hashimoto’s encephalopathy (HE) is a rare autoimmune disorder. It associates encephalopathy with autoimmune thyroiditis, presenting abnormal elevations of thyroid antibodies. It is more common in females. It can present with various symptoms, including seizures, myoclonus, psychosis, hallucinations, and mood disturbances. Hypochondriacal delusion is an unusual clinical presentation of this disorder. The authors report a case of HE in a male patient whose clinical presentation was dominated by hypochondriacal delusion. The absence of response to antipsychotics, high serum antithyroid peroxidase antibodiesof about 199 UI/ml, the normality of magnetic resonance imaging, and improvement with corticosteroids confirmed the diagnosis. This neuroendocrine disorder is often misdiagnosed and it represents a diagnostic challenge for clinicians. It should be considered in patients presenting a refractory or an atypical neuropsychiatric disorder and having a family history of autoimmune disease.
The SHARED Project: A Novel Approach to Engaging African American Men to Address Lung Cancer Disparities
Authors: Watson Karriem S. , Siegel Leilah D. , Henderson Vida A. , Murray Marcus , Chukwudozie I. Beverly , Odell David , Stinson James , Ituah Ose , Ben Levi Josef , Fitzgibbon Marian L. , Kim Sage , Matthews Phoenix
Published: September 2020

Black men are disproportionately impacted by lung cancer morbidity and mortality. Low-dose helical computed tomography (LDCT) lung cancer screening has demonstrated benefits for reducing lung cancer deaths by identifying cancers at earlier, more treatable stages. Despite the known benefits, LDCT screening is underutilized in black men. Studies in racially heterogeneous populations have found correlations between screening behaviors and factors such as physician trust, physician referral, and a desire to reduce the uncertainty of not knowing if they had lung cancer; yet little is known about the factors that specifically contribute to screening behaviors in black men. Community engagement strategies are beneficial for understanding barriers to health-care engagement. One community engagement approach is the citizen scientist model. Citizen scientists are lay people who are trained in research methods; they have proven valuable in increasing communities’ knowledge of the importance of healthy behaviors such as screening, awareness of research, building trust in research, and improving study design and ethics. This paper proposes an intervention, grounded in community-based participatory research approaches and social network theory, to engage black men as citizen scientists in an effort to increase lung cancer screening in black men. This mixed-methods intervention will examine the attitudes, behaviors, and beliefs of black men related to uptake of evidence-based lung cancer screening.
Factors influencing the laser treatment of textile materials: An overview
Authors: Angelova Yordanka P
Published: September 2020

A number of laser treatments in the textile industry such as: marking, engraving, cutting, welding, sintering, three-dimensional scanning, and others, have been successfully applied in recent years. Laser technologies are ones that may be used for decorative or identification marking of products, precise cutting, quality joining by welding both traditional materials and newly developed ones. The use of laser systems for processing of materials, in particular, textile polymers, increases due to the speed, accuracy, and flexibility of this innovative technology. The factors exerting impact over, the laser processing of natural and synthetic textile materials are a lot. They are encountered in certain connections and relationships to each other and affect, to a greater or lesser extent, the quality of the laser processing. The process may be optimized by selecting and managing the most significant factors. Most of them are presented and analyzed in this article aimed at understanding the physical nature of these processes. The factors, which exert the greatest impact on the technological process for laser treatments of textile materials, are indicated.
Remembrance Day for Lost Species: Remembering and mourning extinction in the Anthropocene
Authors: de Massol de Rebetz Clara
Published: September 2020

This article examines what is lost and remembered at a time of mass extinction; identifying the Anthropocene – the geological epoch in which the incremental and disruptive impact of the human species has become the main planetary force – as an epoch of mourning. The paper explores the memory and future memory of extinction through the example of Remembrance Day for Lost Species, an international initiative encouraging people all over the world to gather annually on 30th November in funeral ceremonies to mourn extinct species. The article particularly draws on Ursula Heise’s concept of ‘eco-cosmopolitanism’ (2008, 2016) and Michael Rothberg’s ‘multidirectional memory’ (2009) as well as fieldwork notes and interviews conducted during Lost Species Day 2018 in Brighton, UK. The analysis considers the conditions of future memory at a time of ecological loss by examining the extinction memorial and funerary practices formulated and performed during the Remembrance Day’s events.
Provincializing memory studies: The insistence of the ‘here-now’
Authors: Collins Felicity , Healy Chris , Radstone Susannah
Published: September 2020

This essay responds to Astrid Erll’s question about what it might mean to do memory studies in different parts of the world. We offer a response from the perspective of three researchers based in Australia. Focused on a season-opening gala performance, a photographic series, a site-specific protest, and a film that takes a choir from Central Australia to Germany, the essay tracks the emergence, in culture, of something we term the ‘here-now’. The essay argues that this ‘here-now’ belongs neither to historical temporality’s linear time-line, nor to the cosmology of an unsullied Indigenous culture – and cannot easily be addressed in the language of memory studies. Taking our lead from four case studies, we try to find words for what it is that the ‘here-now’ makes present, as it emerges in the artworks and events we discuss. We find that the ‘here-now’s’ ordering of place/time insistently evokes a yet-to-be realized Australia, while prompting recognition of the hard truths that still stand in its way.
A systematic review of outcomes of wrist arthrodesis and wrist arthroplasty in patients with rheumatoid arthritis
Authors: Zhu Xi Ming , Perera Edward , Gohal Chetan , Dennis Brittany , Khan Moin , Alolabi Bashar
Published: September 2020

Surgical management of end-stage rheumatoid wrists is a contentious topic. The standard surgical treatment has traditionally been wrist arthrodesis. Wrist arthroplasty, however, offers an alternative that preserves some wrist motion. A systematic review of MEDLINE, EMBASE and CENTRAL databases was conducted. Data from 23 studies representing 343 cases of wrist arthrodesis and 618 cases of wrist arthroplasty were included. Complication rates were 17% for arthrodesis and 19% for arthroplasty, and both procedures were effective at alleviating pain and improving grip strength. Functional assessment by Disabilities of the Arm, Shoulder, and Hand and Patient-Related Wrist Evaluation of arthroplasty patients revealed clinically meaningful functional improvement compared with preoperative measurements. In contrast to previously published findings both procedures demonstrated comparable complication rates. While this can be speculated to be from advancements in prosthetics, robust long-term follow-up data on wrist arthroplasty are not available yet.
Anatomic total shoulder arthroplasty in rheumatoid arthritis: A systematic review
Authors: Haleem Ahmed , Shanmugaraj Ajaykumar , Horner Nolan S. , Leroux Timothy , Khan Moin , Alolabi Bashar
Published: September 2020

Purpose

Given the poor soft-tissue quality in rheumatoid arthritis patients, many believe that rheumatoid arthritis should be treated with reverse total shoulder arthroplasty (rTSA). The purpose of this paper is to systematically assess outcomes of anatomic total shoulder arthroplasty (aTSA) in rheumatoid arthritis to determine if aTSA remains a viable option.

Methods

A comprehensive literature search was conducted identifying articles relevant to aTSA in the setting of rheumatoid arthritis with intact rotator cuff. Outcomes include clinical outcomes and rates of complication and revision.

Results

Ten studies were included with a total of 279 shoulders with mean follow-up of 116 ± 69 months. The mean age was 68 ± 10 years. Survivorship was 97%, 97% and 89% at 5, 10 and 20 years, respectively. The overall complication rate was 9%. Radiolucency was present in 69% of patients, of which 34% were at risk of loosening at 79 months. The overall rate of revision was 8.4%. Studies generally reported clinically significant improvements in range of motion, Constant score and ASES score.

Conclusion

aTSA in the rheumatoid patient results in improvements in range of motion and patient-reported outcomes. Rates of complications and survivorship are generally good in this population. However, it should be noted that there is significant heterogeneity in outcome reporting amongst the literature on this topic and that many studies fail to adequately report complication and revision rates. When compared to rTSA in patients with rheumatoid arthritis, evidence suggests that aTSA is still a viable treatment option despite the shift in utilization to rTSA.
Health Literacy in Hospital Outpatient Waiting Areas: An Observational Study of What Is Available to and Accessed by Consumers
Authors: McDonald Cassie E. , Remedios Louisa J. , Said Catherine M. , Granger Catherine L.
Published: September 2020

Aim:

To investigate: (1) the types of health information, resources, and supports available to consumers in hospital outpatient waiting areas and (2) whether these are accessed by consumers.

Background:

Outpatient waiting areas commonly offer health information, resources, and supports to improve the health literacy of waiting consumers. It is not known what is available to or accessed by consumers in hospital outpatient rehabilitation waiting areas.

Methods:

A multicenter, prospective, observational, cross-sectional study was conducted in the waiting areas of two hospital outpatient rehabilitation services. Direct observations (in person and video recordings) of the waiting areas were used to describe what health information, resources, and supports were available and, if present, what was being accessed and for how long by consumers.

Results:

Fifteen hours of in-person and video-recorded observations were documented on purpose-designed instruments across the two sites during 18 observation sessions over 8 days. A total of 68 different health information and resources were identified. Approximately half were specifically for consumers (Site 1: 57%; Site 2: 53%). Only seven (10%) were accessed by consumers across both sites. Each resource ( n = 7) was only accessed once. Health resources were used by consumers for 0.8% (3/360 min) of the observation time at each site. Health and social supports and use of other non health resources were also observed.

Conclusions:

Available health information, resources, and supports were infrequently and briefly accessed by consumers. Further research is required to explore what consumers want and need to improve the health literacy responsiveness of hospital outpatient waiting areas.
Demographics and Epidemiology of Discoid Menisci of the Knee: Analysis of a Large Regional Insurance Database
Authors: Grimm Nathan L. , Pace James Lee , Levy Benjamin J. , Arthur D’Ann , Portman Mark , Solomito Matthew J. , Weiss Jennifer M.
Published: September 2020

Background:

A discoid meniscus is a morphological variant of normal knee joint meniscus shape and ultrastructure that can lead to traumatic tearing of this tissue and early joint osteoarthritis.

Purpose/Hypothesis:

The purpose of this study was to determine the prevalence of discoid menisci in a large, ethnically diverse regional cohort and to evaluate possible risk factors. The hypothesis was that there would be no difference in the epidemiological distribution of discoid menisci based on ethnicity or sex.

Study Design:

Descriptive epidemiology study.

Methods:

The study population was from a regional, integrated health care system cohort from Kaiser Permanente of Southern California that, as of 2016, included more than 4.5 million patients. Patient demographics included age, sex, and ethnicity within this cohort. Potential risk factors analyzed included age, sex, ethnicity, and body mass index (BMI). Unique characteristics of a discoid meniscus were analyzed, including a symptomatic versus asymptomatic meniscus, location of meniscal tear and type of meniscus, and frequency of meniscal surgical treatment.

Results:

A total of 223 patients with a confirmed discoid meniscus were identified, yielding an overall prevalence rate of 4.88 per 100,000 patients. Those identifying as Black had the lowest prevalence (2.68/100,000), while Hispanic ethnicity had the highest (6.01/100,000). However, there was no significant difference with regard to ethnicity ( P = .283), nor any significant difference between sexes. BMI did not significantly influence the rate of discoid menisci ( P = .504). A majority (77.5%) of patients were symptomatic, while 22.5% of patients with discoid menisci were asymptomatic and discovered incidentally. Symptomatic discoid menisci were more likely to be operated on compared with asymptomatic discoid menisci (71% vs 14%, respectively; P = .001; odds ratio, 14.8 [95% CI, 5.8-37.2]). Horizontal and bucket-handle tears were the more common tear types. Of the discoid menisci in this cohort, 55.6% underwent surgery, with 95.2% undergoing reported saucerization.

Conclusion:

In this very diverse population-based cohort of patients, there did not seem to be a significant predilection of discoid menisci with regard to ethnicity. Neither sex nor BMI significantly influenced the rate of discoid menisci. More than three-quarters of those with a diagnosed discoid meniscus were symptomatic. Of the tears that occurred with discoid menisci, horizontal and bucket-handle tears made up the largest proportion.
The traffic signal control problem for intersections: a review
Authors: Eom Myungeun , Kim Byung-In
Published: September 2020

Background

The intersection traffic signal control problem (ITSCP) has become even more important as traffic congestion has been more intractable. The ITSCP seeks an efficient schedule for traffic signal settings at intersections with the goal of maximizing traffic flow while considering various factors such as real-time strategies, signal timing constraints, rapid developments in traffic systems, and practical implementation. Since the factors constituting the ITSCP exhibit stochastically complicated interactions, it is essential to identify these factors to propose solution methods that can address this complexity and still be practically implemented.

Objective

The objective of this review is to provide a survey of problems, methods, and practices in the evaluation of the ITSCP. In this paper, a unified terminology for the ITSCP and a citation network of the current body of relevant research are accordingly presented, and various assumptions, constraints, and solution approaches are summarized. A review across the entire body of knowledge throughout the history of the ITSCP is therefore provided. This review also highlights open issues and challenges that remain to be addressed by future research.
NEDD: a network embedding based method for predicting drug-disease associations
Authors: Zhou Renyi , Lu Zhangli , Luo Huimin , Xiang Ju , Zeng Min , Li Min
Published: September 2020

Background

Drug discovery is known for the large amount of money and time it consumes and the high risk it takes. Drug repositioning has, therefore, become a popular approach to save time and cost by finding novel indications for approved drugs. In order to distinguish these novel indications accurately in a great many of latent associations between drugs and diseases, it is necessary to exploit abundant heterogeneous information about drugs and diseases.

Results

In this article, we propose a meta-path-based computational method called NEDD to predict novel associations between drugs and diseases using heterogeneous information. First, we construct a heterogeneous network as an undirected graph by integrating drug-drug similarity, disease-disease similarity, and known drug-disease associations. NEDD uses meta paths of different lengths to explicitly capture the indirect relationships, or high order proximity, within drugs and diseases, by which the low dimensional representation vectors of drugs and diseases are obtained. NEDD then uses a random forest classifier to predict novel associations between drugs and diseases.

Conclusions

The experiments on a gold standard dataset which contains 1933 validated drug–disease associations show that NEDD produces superior prediction results compared with the state-of-the-art approaches.
GPU acceleration of Darwin read overlapper for de novo assembly of long DNA reads
Authors: Ahmed Nauman , Qiu Tong Dong , Bertels Koen , Al-Ars Zaid
Published: September 2020

Background

In Overlap-Layout-Consensus (OLC) based de novo assembly, all reads must be compared with every other read to find overlaps. This makes the process rather slow and limits the practicality of using de novo assembly methods at a large scale in the field. Darwin is a fast and accurate read overlapper that can be used for de novo assembly of state-of-the-art third generation long DNA reads. Darwin is designed to be hardware-friendly and can be accelerated on specialized computer system hardware to achieve higher performance.

Results

This work accelerates Darwin on GPUs. Using real Pacbio data, our GPU implementation on Tesla K40 has shown a speedup of 109x vs 8 CPU threads of an Intel Xeon machine and 24x vs 64 threads of IBM Power8 machine. The GPU implementation supports both linear and affine gap, scoring model. The results show that the GPU implementation can achieve the same high speedup for different scoring schemes.

Conclusions

The GPU implementation proposed in this work shows significant improvement in performance compared to the CPU version, thereby making it accessible for utilization as a practical read overlapper in a DNA assembly pipeline. Furthermore, our GPU acceleration can also be used for performing fast Smith-Waterman alignment between long DNA reads. GPU hardware has become commonly available in the field today, making the proposed acceleration accessible to a larger public. The implementation is available at https://github.com/Tongdongq/darwin-gpu.
Optimal reference genes for gene expression analysis in polyploid of Cyprinus carpio and Carassius auratus
Authors: Liu Wenbin , Yuan Xiudan , Yuan Shuli , Dai Liuye , Dong Shenghua , Liu Jinhui , Peng Liangyue , Wang Minmeng , Tang Yi , Xiao Yamei
Published: September 2020

Background

Reference genes are usually stably expressed in various cells and tissues. However, it was reported that the expression of some reference genes may be distinct in different species. In this study, we intend to answer whether the expression of reported traditional reference genes changes or not in the polyploid fish

Results

By retrieving the mRNA sequencing data of three different ploidy fish from the NCBI SRA database, we selected 12 candidate reference genes, and examined their expression levels in the 10 tissues and in the four cell lines of three different ploidy fish by real-time PCR. Then, the expression profiles of these 12 candidate reference genes were systematically evaluated by using the software platforms: BestKeeper, NormFinder and geNorm.

Conclusion

The 28S ribosomal protein S5 gene (RPS5) and the ribosomal protein S18 gene (RPS18) are the most suitable reference genes for the polyploid of Cyprinus carpio and Carassius auratus, demonstrated by both of the tissues and the cultured cells.
EttA is likely non-essential in Staphylococcus aureus persistence, fitness or resistance to antibiotics
Authors: Meir Michal , Rozenblit Anna , Fliger Simona , Geffen Yuval , Barkan Daniel
Published: September 2020

Background

Tolerance to antibiotics and persistence are associated with antibiotic treatment failures, chronic-relapsing infections, and emerging antibiotic resistance in various bacteria, including Staphylococcus aureus. Mechanisms of persistence are largely unknown, yet have been linked to physiology under low-ATP conditions and the metabolic-inactive state. EttA is an ATP-binding cassette protein, linked in Eschrechia coli to ribosomal hibernation and fitness in stationary growth phase, yet its role in S. aureus physiology is unknown.

Results

Using whole genome sequencing (WGS) of serial clinical isolates, we identified an EttA-negative S. aureus mutant (ettAstop), and its isogenic wild-type counterpart. We used these two isogenic clones to investigate the role of ettA in S. aureus physiology in starvation and antibiotic stress, and test its role in persistence and antibiotic tolerance. ettAstop and its WT counterpart were similar in their antibiotic resistance profiles to multiple antibiotics. Population dynamics of ettAstop and the WT were similar in low-nutrient setting, with similar recovery from stationary growth phase or starvation. Supra-bacteriocidal concentration of cefazolin had the same killing effect on ettAstop and WT populations, with no difference in persister formation.

Conclusions

Lack of ettA does not affect S. aureus antibiotic resistance, beta-lactam tolerance, resilience to starvation or fitness following starvation. We conclude the role of ettA in S. aureus physiology is limited or redundant with another, unidentified gene. WGS of serial clinical isolates may enable investigation of other single genes involved in S. aureus virulence, and specifically persister cell formation.
NGF receptors and PI3K/AKT pathway involved in glucose fluctuation-induced damage to neurons and α-lipoic acid treatment
Authors: Yan Ting , Zhang Zhihui , Li Danqing
Published: September 2020

Background

Glucose fluctuation promotes neuronal apoptosis, which plays a central role in diabetic encephalopathy (DE). Nerve growth factor (NGF), and its interaction with high-affinity (TrkA) and low-affinity (p75NTR) receptors, are involved in neuronal survival. NGF/TrkA contributes to the activation of the PI3K/AKT pathway, which is beneficial for neuronal survival, and α-Lipoic acid (ALA) exerts clinically favorable neuroprotective effects in the periphery. Whether NGF receptors and the PI3K/AKT pathway are involved in glucose fluctuation-induced neuronal damage, as well as the potential molecular mechanism of ALA in protecting glucose fluctuation-induced neuronal damage, remain unclear.

Results

The results indicated that constant high glucose (CHG) and intermittent high glucose (IHG) significantly increased the expression of Bax and caspase-3, and decreased the expression of TrkA/p75NTR and p-AKT/AKT, while ALA stimulation reversed the above proteins in PC12 cells. IHG stimulates apoptosis more effectively than CHG in PC12 cells, which is related to the PI3K/AKT pathway but not to the TrkA/p75NTR. Furthermore, neuronal apoptosis induced by IHG was aggravated by the TrkA inhibitor K252a or the PI3K/AKT inhibitor LY294002, but this effect was alleviated by the p75NTR inhibitor TAT-pep5.

Conclusion

Glucose fluctuation induced cell apoptosis by regulating the TrkA/p75NTR and PI3K/AKT pathway, meanwhile ALA exhibited neuroprotective effects in response to IHG and CHG. These observations indicated that the PI3K/AKT pathway and the balance of TrkA/p75NTR are likely to serve as potential therapeutic targets for DE. In addition, ALA could be a possible therapeutic drug for DE.
Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study
Authors: Jung Jongtak , Song Kyoung-Ho , Jun Kang Il. , Kang Chang Kyoung , Kim Nak-Hyun , Choe Pyoeng Gyun , Park Wan Beom , Bang Ji Hwan , Kim Eu Suk , Park Sang-Won , Kim Nam Joong , Oh Myoung-don , Kim Hong Bin
Published: September 2020

Background

Although the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases.

Methods

All adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly.

Results

Out of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (− 1), and adequate source control (− 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (− 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806–0.916) and 0.792 (95CI, 0.724–0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively.

Conclusions

FUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores—which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups—had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.
A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report
Authors: Jacob Arthur , Pasquier Jennifer , Carapito Raphael , Auradé Frédéric , Molitor Anne , Froguel Philippe , Fakhro Khalid , Halabi Najeeb , Viot Géraldine , Bahram Seiamak , Rafii Arash
Published: September 2020

Background

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in theEFTUD2gene.

Case presentation

Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in theEFTUD2gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon.

Conclusions

We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.
Whole-exome sequencing reveals ANO8 as a genetic risk factor for intrahepatic cholestasis of pregnancy
Authors: Liu Xianxian , Lai Hua , Zeng Xiaoming , Xin Siming , Nie Liju , Liang Zhenyi , Wu Meiling , Chen Yu , Zheng Jiusheng , Zou Yang
Published: September 2020

Background

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and cholestasis in late pregnancy and results in adverse pregnancy outcomes, including preterm delivery and birth weight, which are affected by the genetic and environmental background. However, until now, the genetic architecture of ICP has remained largely unclear.

Methods

Twenty-six clinical data points were recorded for 151 Chinese ICP patients. The data generated from whole-exome sequencing (WES) using the BGISEQ-500 platform were further analyzed by Burrows-Wheeler Aligner (BWA) software, Genome Analysis Toolkit (GATK), ANNOVAR tool, etc. R packages were used to conduct t-test, Fisher’s test and receiver operating characteristic (ROC) curve analyses.

Results

We identified eighteen possible pathogenic loci associated with ICP disease in known genes, covering ABCB4, ABCB11, ATP8B1 and TJP2. The loci Lys386Gln, Gly527Gln and Trp708Ter in ABCB4, Leu589Met, Gln605Pro and Gln1194Ter in ABCB11, and Arg189Ser in TJP2 were novel discoveries. In addition, WES analysis indicated that the gene ANO8 involved in the transport of bile salts is newly identified as associated with ICP. The functional network of the ANO8 gene confirmed this finding. ANO8 contained 8 rare missense mutations that were found in eight patients among the 151 cases and were absent from 1029 controls. Out of the eight SNPs, 3 were known, and the remaining five are newly identified. These variants have a low frequency, ranging from 0.000008 to 0.00001 in the ExAC, gnomAD – Genomes and TOPMED databases. Bioinformatics analysis showed that the sites and their corresponding amino acids were both highly conserved among vertebrates. Moreover, the influences of all the mutations on protein function were predicted to be damaging by the SIFT tool. Combining clinical data, it was found that the mutation group (93.36 µmol/L) had significantly (P = 0.038) higher total bile acid (TBA) levels than the wild-type group (40.81 µmol/L).

Conclusions

To the best of our knowledge, this is the first study to employ WES technology to detect genetic loci for ICP. Our results provide new insights into the genetic basis of ICP and will benefit the final identification of the underlying mutations.
Exploring health literacy in Wuhan, China: a cross-sectional analysis
Authors: Mei Xin , Zhong Qing , Chen Gong , Huang Yuanxia , Li Junlin
Published: September 2020

Background

In recent years, research on health literacy has become increasingly focused on the health care system and public health. This cross-sectional study aimed to investigate health literacy and analyse the risk factors that affect health literacy in Wuhan, China.

Methods

Multistage stratified random sampling was used to select 5304 urban and rural residents aged 15 to 69 years from 204 monitoring points in 15 districts of Wuhan. Using the Chinese Citizen Health Literacy Questionnaire (HLQ) (2018 edition), a face-to-face survey was conducted from November to December 2018. Risk factors that may affect health literacy were assessed using the Chi-square test and multivariate logistic regression models.

Results

The knowledge rate of health literacy was relatively low (19.3%). The knowledge rate of health-related behaviour and lifestyle (BAL, 17.3%) was the lowest of the three aspects of health literacy, and the knowledge rate of chronic diseases (CD, 19.0%) was the lowest of the six dimensions of health literacy. Respondents who lived in urban areas, had higher education levels, worked as medical staff, had a higher household income and did not suffer from chronic diseases were likely to have higher health literacy.

Conclusions

The health literacy levels of citizens in Wuhan are insufficient and need to improve.
Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials
Authors: Singh Dave , Wedzicha Jadwiga A. , Siddiqui Salman , de la Hoz Alberto , Xue Wenqiong , Magnussen Helgo , Miravitlles Marc , Chalmers James D. , Calverley Peter M. A.
Published: September 2020

Background

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.

Methods

This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.

Results

Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150–300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150–300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150–300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).

Conclusion

We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.

Trial registration

ClinicalTrials.govIdentifiers:NCT00168844,NCT00168831,NCT00387088,NCT00782210,NCT00782509,NCT00793624,NCT00796653,NCT01431274,NCT01431287,NCT02296138andNCT00975195.

Graphical abstract
The effects of nudges on purchases, food choice, and energy intake or content of purchases in real-life food purchasing environments: a systematic review and evidence synthesis
Authors: Harbers Marjolein C. , Beulens Joline W. J. , Rutters Femke , de Boer Femke , Gillebaart Marleen , Sluijs Ivonne , van der Schouw Yvonne T.
Published: September 2020

Background

Adults with a low socioeconomic position (SEP) are more likely to engage in unhealthy diets as compared to adults with high SEP. However, individual-level educational interventions aiming to improve food choices have shown limited effectiveness in adults with low SEP. Environmental-level interventions such as nudging strategies however, may be more likely to benefit low SEP groups. We aimed to review the evidence for the effectiveness of nudges as classified according to interventions in proximal physical micro-environments typology (TIPPME) to promote healthy purchases, food choice, or affecting energy intake or content of purchases, within real-life food purchasing environments. Second, we aimed to investigate the potentially moderating role of SEP.

Methods

We systematically searched PubMed, EMBASE, and PsycINFO until 31 January 2018. Studies were considered eligible for inclusion when they i) complied with TIPPME intervention definitions; ii) studied actual purchases, food choice, or energy intake or content of purchases, iii) and were situated in real-life food purchasing environments. Risk of bias was assessed using a quality assessment tool and evidence was synthesized using harvest plots.

Results

From the 9210 references identified, 75 studies were included. Studies were generally of weak to moderate quality. The most frequently studied nudges were information (56%), mixed (24%), and position nudges (13%). Harvest plots showed modest tendencies towards beneficial effects on outcomes for information and position nudges. Less evidence was available for other TIPPME nudging interventions for which the harvest plots did not show compelling patterns. Only six studies evaluated the effects of nudges across levels of SEP (e.g., educational level, food security status, job type). Although there were some indications that nudges were more effective in low SEP groups, the limited amount of evidence and different proxies of SEP used warrant caution in the interpretation of findings.

Conclusions

Information and position nudges may contribute to improving population dietary behaviours. Evidence investigating the moderating role of SEP was limited, although some studies reported greater effects in low SEP subgroups. We conclude that more high-quality studies obtaining detailed data on participant’s SEP are needed.

Registration

This systematic review is registered in the PROSPERO database (CRD42018086983).
Drug use disorder following early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study
Authors: Aschengrau Ann , Grippo Alexandra , Winter Michael R. , Shea Margaret G. , White Roberta F. , Saitz Richard
Published: September 2020

Background

Many studies of adults with occupational exposure to solvents such as tetrachloroethylene (PCE) have shown adverse effects on cognition, mood and behavioral problems. Much less is known about neurotoxic effects in early life at lower exposure levels seen in community settings. We recently reported that illicit drug use was more frequent among adults from Cape Cod, Massachusetts who were exposed to PCE-contaminated drinking water during gestation and early childhood than their unexposed counterparts. Using newly collected data from this population-based retrospective cohort study, the current analysis examines whether early life PCE exposure is also associated with drug use disorder over the life course.

Methods

Three-hundred and sixty-three subjects with prenatal and early childhood PCE exposure and 255 unexposed subjects were studied. These individuals (median age: 40–41 years) completed self-administered questionnaires on the eleven established diagnostic criteria for drug use disorder and confounding variables. A validated leaching and transport model was used to estimate exposure to PCE-contaminated water.

Results

Overall, 23.3% of subjects reported having at least one criterion for drug use disorder over their lifetime. Early life PCE exposure was associated with a modest increase in the lifetime presence of one or more diagnostic criteria for drug use disorder (adjusted RR: 1.4, 95% CI: 1.0–1.8). Compared to unexposed subjects, PCE-exposed subjects were more likely to report having most diagnostic criteria of drug use disorder, including neglecting major roles due to drug use, physical and psychological problems related to drug use, and giving up activities due to drug use. No dose-response relationships were observed with increasing levels of PCE exposure.

Conclusions

These results suggest that exposure to PCE-contaminated drinking water during early life modestly increases the risk of developing diagnostic criteria for drug use disorder later in life. Because this study has several limitations, these findings should be confirmed in follow-up investigations of other exposed populations with more diverse racial and socioeconomic characteristics.
Correlation between exposure to fine particulate matter and hypertensive disorders of pregnancy in Shanghai, China
Authors: Su Xiujuan , Zhao Yan , Yang Yingying , Hua Jing
Published: September 2020

Background

Association between fine particulate matter (PM2.5) and hypertensive disorders of pregnancy (HDP) is inconsistent and appears to change in each trimester. We aim to investigate the association of exposure to ambient PM2.5 in early pregnancy with HDP.

Methods

A retrospective cohort study was performed among 8776 women with singleton pregnancy who attended the antenatal clinic before 20 gestational weeks in a tertiary women’s hospital during 2014–2015. Land use regression models were used to predict individual levels of PM2.5 exposure.

Results

The average PM2.5 concentration during the first 20 gestational weeks ranged from 28.6 to 74.8 μg m− 3 [median, 51.4 μg m− 3; interquartile range, 47.3–57.8 μg m− 3]. A total of 440 (5.0%) women was diagnosed with HDP. The restricted cubic spline showed a positive exposure-response relationship between the PM2.5 concentration and risk of HDP. We observed an association between PM2.5 exposure during the first trimester with HDP (RR = 3.89 per 10 μg m− 3, 95% CI: 1.45–10.43), but not during the second trimester (RR = 0.71 per 10 μg m− 3, 95% CI: 0.40–1.27). Compared with their counterparts, nulliparous women who were exposed to high levels of PM2.5 in the index pregnancy had a higher risk of developing HDP [the relative excess risk due to interaction was 0.92 (0.46–1.38)].

Conclusion

Our findings suggest that PM2.5 exposure during the first trimester is associated with the development of HDP. The effect estimate is more obvious for nulliparous women than multiparous women.
Beta-lactams susceptibility testing of penicillin-resistant, ampicillin-susceptible Enterococcus faecalis isolates: a comparative assessment of Etest and disk diffusion methods against broth dilution
Authors: Conceição Natália , Rodrigues Wellington Francisco , de Oliveira Kessys Lorrânya Peralta , da Silva Lucas Emanuel Pinheiro , de Souza Laís Rezende Cardoso , da de Cunha Hueb Barata Oliveira Cristina , de Oliveira Adriana Gonçalves
Published: September 2020

This study aimed to evaluate the accuracy of disk diffusion and Etest methods, compared to that of the broth dilution reference method for identifying beta-lactam susceptibilities of Penicillin-Resistant, Ampicillin-SusceptibleEnterococcus faecalis(PRASEF) isolates. Fifty-nine PRASEF and 15 Penicillin-Susceptible, Ampicillin-SusceptibleE. faecalis(PSASEF) clinical nonrepetitive isolates were evaluated. The effectiveness of five beta-lactams (ampicillin, amoxicillin, imipenem, penicillin, and piperacillin) was tested. All antimicrobial susceptibility tests were performed and interpreted according to the Clinical and Laboratory Standards Institute guidelines. Interpretative discrepancies, such as essential agreement, categorical agreement, and errors, were assessed. The acceptability was ≥ 90% for both categorical agreement and essential agreement. Etest proved to be an accurate method for testing beta-lactam susceptibilities of the emerging PRASEF isolates, disk diffusion presented poor performance, particularly for imipenem and piperacillin.
Coordinating the research response to COVID-19: Mali’s approach
Authors: Doumbia Seydou , Sow Ydrissa , Diakite Mahamadou , Lau Chuen-Yen
Published: September 2020

Mali, like the rest of the world, has seen a rapid spread of COVID-19 since the first report of imported cases. Despite being a low-income country, Mali has leveraged scientific research resources via coordinated approaches to enable public health emergency planning and response to the COVID-19 pandemic. Mali’s approach includes the harmonization of research activities; leveraging of research laboratory capacity of the University Clinical Research Center, Mali International Center for Excellence and three other in-country laboratories for community COVID-19 testing; strengthening relationships amongst local and international stakeholders; and collaboration with the Ministry of Health to integrate scientific evidence into public policy and emergency management of COVID-19 through a platform of consultation and open communication. The country has implemented national coordination of its COVID-19 response by establishing a COVID-19 Scientific Advisory Committee and a COVID-19 Technical Coordination Committee, both within the Ministry of Health and working collaboratively with other stakeholders. Members of Mali’s COVID-19 Scientific Advisory Committee also serve as leaders of its principal academic and government clinical and public health research entities. This centralised approach has enabled the prioritisation of COVID-19 control activities, informed allocation of resources, evidence-based public health practices and timely decision-making in the pandemic setting. Though challenges remain, lessons learned from Mali’s harnessing of clinical research capacity to guide and support its COVID-19 response can be applied to future global health research challenges and illustrate the power of building public health-responsive research capacity in resource-limited settings through international collaboration.