bluuebunny/crossref_metadata_2025 huggingface dataset:
Vanillin Production in
Pseudomonas
: Whole-Genome Sequencing of
Pseudomonas
sp. Strain 9.1 and Reannotation of Pseudomonas putida CalA as a Vanillin Reductase
Authors: García-Hidalgo Javier , Brink Daniel P. , Ravi Krithika , Paul Catherine J. , Lidén Gunnar , Gorwa-Grauslund Marie F.
Published: January 2020

Valorization of lignocellulose (nonedible plant matter) is of key interest for the sustainable production of chemicals from renewable resources. Lignin, one of the main constituents of lignocellulose, is a heterogeneous aromatic biopolymer that can be chemically depolymerized into a heterogeneous mixture of aromatic building blocks; those can be further converted by certain microbes into value-added aromatic chemicals, e.g., the flavoring agent vanillin. We previously isolated a
Pseudomonas
sp. strain with the (for the genus) unusual trait of vanillyl alcohol production during growth on vanillin. Whole-genome sequencing of the isolate led to the identification of a vanillin reductase candidate gene whose deletion in a recombinant vanillin-accumulating
P. putida
strain almost completely alleviated the undesired vanillyl alcohol by-product yield. These results represent an important step toward biotechnological production of vanillin from lignin using bacterial cell factories.
Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment
Authors: Nayak Abhijeet , Schüler Wolfgang , Seidel Stefan , Gomez Ivan , Meinke Andreas , Comstedt Pär , Lundberg Urban
Published: January 2020

The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, development might be restricted either to conserved antigens, which are often rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the United States and Europe.
Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing
Authors: Götte Benjamin , Utt Age , Fragkoudis Rennos , Merits Andres , McInerney Gerald M.
Published: January 2020

Old World alphaviruses comprise several medically relevant viruses, including chikungunya virus and Ross River virus. Recurrent outbreaks and the lack of antivirals and vaccines demand ongoing research to fight the emergence of these infectious diseases. In this context, a thorough investigation of virus-host interactions is critical. Here, we highlight the importance of the host protein G3BP for several Old World alphaviruses. Our data strongly suggest that G3BP plays a crucial role for the activity of the viral replicase and, thus, the amplification of the viral RNA genome. To our knowledge, the present work is the first to provide a functional link between the regulation of viral polyprotein processing and RNA replication and a host factor for alphaviruses. Moreover, the results of this study raise several questions about the fundamental regulatory mechanisms that dictate the activity of the viral replicase, thereby paving the way for future studies.
B Cell-Specific Transcription Activator PAX5 Recruits p300 To Support EBNA1-Driven Transcription
Authors: Liu Cheng-Der , Lee Hsueh-Ling , Peng Chih-Wen
Published: January 2020

Although B cells are known to be the primary target for EBV infection, there is limited knowledge regarding the mechanism that determines this preferable tissue tropism. An in-depth understanding of the potential link of tissue-specific factors with the viral genes and their functioning is key to deciphering how EBV induces persistent infection in the distinct types of host cells. In this study, a substantial protein-protein interaction mediated by the B cell-specific activator PAX5 and EBNA1 was identified as the general requirement for the binding of EBNA1 to the latent replication origin and for downstream events. Of importance, the EBNA1-PAX5-p300 network is directly linked to EBNA1-dependent transcription. These findings suggest that targeting the viral gene-associated tissue-specific factors may lead to new therapeutic strategies for EBV-associated malignancies.
A CRISPR Interference System for Efficient and Rapid Gene Knockdown in Caulobacter crescentus
Authors: Guzzo Mathilde , Castro Lennice K. , Reisch Christopher R. , Guo Monica S. , Laub Michael T.
Published: January 2020

Caulobacter crescentus
is a major model organism for understanding cell cycle regulation and cellular asymmetry. The current genetic tools for deleting or silencing the expression of individual genes, particularly those essential for viability, are time-consuming and labor-intensive, which limits global genetic studies. Here, we optimized CRISPR interference (CRISPRi) for use in
Caulobacter
. Using
Streptococcus thermophilus
CRISPR3 or
Streptococcus pasteurianus
CRISPR systems, we show that the coexpression of a catalytically dead form of Cas9 (dCas9) with a single guide RNA (sgRNA) containing a seed region that targets the promoter region of a gene of interest efficiently downregulates the expression of the targeted gene. We also demonstrate that multiple sgRNAs can be produced in parallel to enable the facile silencing of multiple genes, opening the door to systematic genetic interaction studies. In sum, our work now provides a rapid, specific, and powerful new tool for silencing gene expression in
C. crescentus
and possibly other alphaproteobacteria.
The Tip of the VgrG Spike Is Essential to Functional Type VI Secretion System Assembly in
Acinetobacter baumannii
Authors: Lopez Juvenal , Ly Pek Man , Feldman Mario F.
Published: January 2020

Despite the clinical relevance of
A. baumannii
, little is known about its fundamental biology. Here, we show that a single amino acid mutation in VgrG, a critical T6SS structural protein, abrogates T6SS function. Given that this mutation was found in a clinical isolate, we propose that the T6SS of
A. baumannii
is probably not involved in virulence; this idea is supported by multiple genomic analyses showing that the majority of clinical
A. baumannii
strains lack proteins essential to the T6SS. We also show that, unlike in other species, the C terminus of VgrG is a unique architectural requirement for functional T6SS assembly in
A. baumannii
, suggesting that over evolutionary time, bacteria have developed changes to their T6SS architecture, leading to specialized systems.
Unique Microbial Catabolic Pathway for the Human Core
N
-Glycan Constituent Fucosyl-α-1,6-
N
-Acetylglucosamine-Asparagine
Authors: Becerra Jimmy E. , Rodríguez-Díaz Jesús , Gozalbo-Rovira Roberto , Palomino-Schätzlein Martina , Zúñiga Manuel , Monedero Vicente , Yebra María J.
Published: January 2020

The gastrointestinal tract accommodates more than 10
14
microorganisms that have an enormous impact on human health. The mechanisms enabling commensal bacteria and administered probiotics to colonize the gut remain largely unknown. The ability to utilize host-derived carbon and energy resources available at the mucosal surfaces may provide these bacteria with a competitive advantage in the gut. Here, we have identified in the commensal species
Lactobacillus casei
a novel metabolic pathway for the utilization of the glycoamino acid fucosyl-α-1,6-
N
-GlcNAc-Asn, which is present in the core-fucosylated
N
-glycoproteins from mammalians. These results give insight into the molecular interactions between the host and commensal/probiotic bacteria and may help to devise new strategies to restore gut microbiota homeostasis in diseases associated with dysbiotic microbiota.
A Bispecific Antibody That Simultaneously Recognizes the V2- and V3-Glycan Epitopes of the HIV-1 Envelope Glycoprotein Is Broader and More Potent than Its Parental Antibodies
Authors: Davis-Gardner Meredith E. , Alfant Barnett , Weber Jesse A. , Gardner Matthew R. , Farzan Michael
Published: January 2020

Broadly neutralizing antibodies (bNAbs) can prevent a new HIV-1 infection and can at least temporarily suppress an established infection. However, antibody-resistant viruses rapidly emerge in infected persons treated with any single bNAb. Several bispecific antibodies have been developed to increase the breadth of these antibodies, but typically only one arm of these bispecific constructs binds the HIV-1 envelope glycoprotein trimer (Env). Here, we develop and characterize bispecific constructs based on well-characterized V2-glycan and V3-glycan bNAbs and show that at least one member of this class is more potent than its parental antibodies, indicating that they can simultaneously bind both of these epitopes of a single Env trimer. These data show that bispecific antibody-like proteins can achieve greater neutralization potency than the bNAbs from which they were derived.
Stochastic Expression of Sae-Dependent Virulence Genes during Staphylococcus aureus Biofilm Development Is Dependent on SaeS
Authors: DelMain Elizabeth A. , Moormeier Derek E. , Endres Jennifer L. , Hodges Rebecca E. , Sadykov Marat R. , Horswill Alexander R. , Bayles Kenneth W.
Published: January 2020

Staphylococcus aureus
is an important human pathogen capable of colonizing diverse tissue types and inducing severe disease in both immunocompromised and otherwise healthy individuals. Biofilm infections caused by this bacterial species are of particular concern because of their persistence, even in the face of intensive therapeutic intervention. The results of the current study demonstrate the stochastic nature of Sae-mediated virulence gene expression in
S. aureus
and indicate that this regulatory system may function as a “bistable switch” in a manner similar to that seen with regulators controlling competence gene expression in
Bacillus subtilis
and persister cell formation in
Escherichia coli
. The results of this study provide a new perspective on the complex mechanisms utilized by
S. aureus
during the establishment of infections.
Network Analysis of the Papaya Orchard Virome from Two Agroecological Regions of Chiapas, Mexico
Authors: Alcalá-Briseño Ricardo I. , Casarrubias-Castillo Kena , López-Ley Diana , Garrett Karen A. , Silva-Rosales Laura
Published: January 2020

Virus-virus interactions in plants can modify host symptoms. As a result, disease management strategies may be unsuccessful if they are based solely on visual assessment and diagnostic assays for known individual viruses. Papaya ringspot virus is an important limiting factor for papaya production and likely has interactions with other viruses that are not yet known. Using high-throughput sequencing, we recovered known and novel RNA and DNA viruses from papaya orchards in Chiapas, Mexico, and categorized them by host and, in the case of papaya, symptom type: asymptomatic papaya, papaya with ringspot virus symptoms, papaya with nonringspot symptoms, weeds, and insects. Using network analysis, we demonstrated virus associations within and among host types and described the ecological community patterns. Recovery of viruses from weeds and asymptomatic papaya suggests the need for additional management attention. These analyses contribute to the understanding of the community structure of viruses in the agroecological landscape.
Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer
Authors: Tomkovich Sarah , Gharaibeh Raad Z. , Dejea Christine M. , Pope Jillian L. , Jiang Jinmai , Winglee Kathryn , Gauthier Josee , Newsome Rachel C. , Yang Ye , Fodor Anthony A. , Schmittgen Thomas D. , Sears Cynthia L. , Jobin Christian
Published: January 2020

Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact growth and gene expression of members of the intestinal microbiota. This study examined the bacteria and bacterial transcriptome associated with microbes derived from biofilm-positive human cancers that promoted tumorigenesis in a murine model of CRC. The murine response to different microbial communities (derived from CRC patients or healthy people) was evaluated through RNA and microRNA sequencing. We identified a complex interplay between biofilm-associated bacteria and the host during CRC in mice. These findings may lead to the development of new biomarkers and therapeutics for identifying and treating biofilm-associated CRCs.
Network-Based Prediction of Novel CRISPR-Associated Genes in Metagenomes
Authors: Weissman J. L. , Johnson Philip L. F.
Published: January 2020

Every branch on the tree of life, including microbial life, faces the threat of viral pathogens. Over the course of billions of years of coevolution, prokaryotes have evolved a great diversity of strategies to defend against viral infections. One of these is the CRISPR adaptive immune system, which allows microbes to “remember” past infections in order to better fight them in the future. There has been much interest among molecular biologists in CRISPR immunity because this system can be repurposed as a tool for precise genome editing. Recently, a number of comparative genomics approaches have been used to detect novel CRISPR-associated genes in databases of genomes with great success, potentially leading to the development of new genome-editing tools. Here, we developed novel methods to search for these distinct classes of genes directly in environmental samples (“metagenomes”), thus capturing a more complete picture of the natural diversity of CRISPR-associated genes.
Hereditary transthyretin amyloidosis caused by the rare Phe33Leu mutation
Authors: Björkenheim Anna , Szabó Barna , Sztaniszláv Áron József
Published: January 2020

Hereditary transthyretin amyloidosis is a rare progressive systemic disease. We describe a physically active 46-year-old man who presented with dyspnoea on exertion. An echocardiogram showed increased left ventricular wall thickness and diastolic dysfunction, but normal systolic function. The QRS voltage on ECG was normal. The patient was diagnosed with hypertrophic cardiomyopathy, and several years passed before establishment of the accurate diagnosis of hereditary transthyretin amyloidosis caused by the rare mutation ATTR Phe33Leu, previously described in only five case reports. Further investigation revealed neuropathy and nephropathy, and the patient developed severe heart failure. The patient is treated with tafamidis, has undergone heart transplantation and is currently planned for liver transplant. Hereditary transthyretin amyloidosis is likely underdiagnosed, especially in patients presenting with cardiomyopathy. A discrepancy between the left ventricular mass indicated by echocardiogram and that on ECG is an important indicator of amyloidosis, as is involvement of multiple organs.
Efficacy of a topical herbal and mineral formulation (Dynamiclear) for the treatment of herpes simplex labialis in the community setting: study protocol for a randomised, double-blind placebo-controlled trial
Authors: Armour Mike , Semprini Alex , Ee Carolyn , MacCullagh Lois , Shortt Nick
Published: January 2020

Introduction

Herpes simplex labialis (HSL) is a common infection that can cause painful lesions on the oral mucosa, commonly referred to as cold sores. Current biomedical treatments include topical aciclovir, which reduces the episode duration by an average of 0.5 days. This study will examine the efficacy and tolerability of an over-the-counter topical treatment, Dynamiclear in reducing duration and severity of HSL episodes.

Methods and analysis

This prospective, randomised, double-blind, placebo-controlled, multi-centre trial will recruit a minimum of 292 adult participants across Australia and New Zealand who present with a cold sore within 48 hours of onset. They will be randomly allocated in a 2:1 ratio to receive either topical Dynamiclear (active) or placebo. Dynamiclear’s active ingredients areHypericum perforatum,Calendula Officinalisand copper sulfate. A single topical treatment of active or placebo will be applied by a pharmacy-based investigator, and participants will be provided with a viral swab kit to confirm presence of herpes virus 1 or 2 from ulcerated lesions. Participants will receive reminders by email and/or SMS to complete an online daily diary assessing their cold sore lesion using a visual guide, and recording other symptoms on numeric scales until healed. The primary outcome variable is median duration of HSL episode in days (participant evaluated) from presentation to return to normal skin. Secondary outcomes include severity of lesion pain, itching, burning and tingling during the symptomatic phase and proportion of lesions progressing to ulceration.

Ethics and dissemination

Australian ethics approval from Western Sydney University Human Research Ethics Committee, ref: H12776. New Zealand Ethics approval from The Health and Disability Ethics Committees (HDEC) ref: 18/CEN/151. Results will be published in a peer-reviewed academic journal, presented at academic meetings and reported to participants

Trial registration numbers

Australia and New Zealand Clinical Trials Registry (ACTRN12618000890235); Universal Trial Number (UTN) (U1111-1233-2426).
Protocol for a prospective, controlled, cross-sectional, diagnostic accuracy study to evaluate the specificity and sensitivity of ambulatory monitoring systems in the prompt detection of hypoxia and during movement
Authors: Areia Carlos , Vollam Sarah , Piper Philippa , King Elizabeth , Ede Jody , Young Louise , Santos Mauro , Pimentel Marco A F , Roman Cristian , Harford Mirae , Shah Akshay , Gustafson Owen , Rowland Matthew , Tarassenko Lionel , Watkinson Peter J
Published: January 2020

Introduction

Automated continuous ambulatory monitoring may provide an alternative to intermittent manual vital signs monitoring. This has the potential to improve frequency of measurements, timely escalation of care and patient safety. However, a major barrier to the implementation of these wearable devices in the ward environment is their uncertain reliability, efficiency and data fidelity. The purpose of this study is to test performance of selected devices in a simulated clinical setting including during movement and low levels of peripheral oxygen saturation.

Methods and analysis

This is a single centre, prospective, controlled, cross-sectional, diagnostic accuracy study to determine the specificity and sensitivity of currently available ambulatory vital signs monitoring equipment in the detection of hypoxia and the effect of movement on data acquisition. We will recruit up to 45 healthy volunteers who will attend a single study visit; starting with a movement phase and followed by the hypoxia exposure phase where we will gradually decrease saturation levels down to 80%. We will simultaneously test one chest patch, one wrist worn only and three wrist worn with finger probe devices against ‘clinical standard ‘and ‘gold standard’ references. We will measure peripheral oxygen saturations, pulse rate, heart rate and respiratory rate continuously and arterial blood gases intermittently throughout the study.

Ethics and dissemination

This study has received ethical approval by the East of Scotland Research Ethics Service REC 2 (19/ES/0008). The results will be broadly distributed through conference presentations and peer-reviewed publications.

Trial registration number

ISRCTN61535692registered on 10/06/2019.
Palliative care for non-cancer conditions in primary care: a time trend analysis in the UK (2009–2014)
Authors: Gadoud Amy , Kane Eleanor , Oliver Steven Edward , Johnson Miriam J , Macleod Una , Allgar Victoria
Published: January 2020

Objectives

While guidelines recommend palliative care in non-cancer conditions, this has not been widely implemented. We examined whether the recording of a palliative care approach and the numbers of hospital deaths for deceased patients with heart failure, dementia, chronic obstructive pulmonary disease (COPD) and cancer have changed since the UK End-of-Life Care Strategy was introduced.

Methods

We conducted sequential cross-sectional studies of decedents within the UK’s Clinical Practice Research Datalink and Hospital Episode Statistics. All adults with a primary care record of COPD (n=5426), dementia (n=7339), heart failure (n=6409) or cancer (n=18 668) who died during three 1 year periods (April 2009 to March 2014) were included. Evidence of a palliative care approach was identified from primary care records, and death in hospital from secondary care data.

Results

From 2009 to 2014, proportions with a primary care record of palliative care increased for COPD from 13.6% to 21.2%; dementia from 20.9% to 40.7%; and heart failure from 12.6% to 21.2%; but remained substantially lower than for cancer (57.6% to 61.9%). Median days before death of recording improved for COPD (145 to 224) and dementia (44 to 209); but not for heart failure (168.5 to 153) and cancer (123 to 114). Trends in hospital deaths were not consistently downward, although the proportions of patients dying in hospital were lower in the last period compared with the first.

Conclusions

Recording of a palliative care approach for non-cancer conditions has increased since the introduction of the UK End-of-Life Care Strategy, but remains inadequate.
Measuring patient and carer experience related to paediatric gastrointestinal endoscopy: multicentre questionnaire study
Authors: Wan Jessica Wai Yan , Griffiths Elizabeth , Rabone Rosalind , Zuhair Zahmeena , Londt Zuzana , Rawat David , Maginnis Janis , Elzubair Amal , Pigott Anna , Thomson Mike , Narula Priya
Published: January 2020

Background

The Paediatric Endoscopy Global Rating Scale (P-GRS) is a quality improvement tool used in the UK. An important aspect of this includes regular surveys on the patient and/or carer’s endoscopy experience. The aim of our study was to design and implement a patient/carer experience questionnaire.

Methods

This questionnaire was designed to obtain feedback on patient and/or carer satisfaction with their endoscopy experience. Question selection was based on relevant measures in the endoscopy Global Rating Scale, with input from clinical governance, Patient Advice and Liaison Service and a hospital youth forum. This was distributed to patients and/or carers in three UK paediatric endoscopy services during six surveys between 2013 and 2018. Data were then collated and analysed on Microsoft Excel for Office 365 MSO (16.0.11901.20070).

Results

Overall, 830 endoscopic procedures occurred during the six survey periods. 270 questionnaires were returned. Feedback from the questionnaires were mostly positive (overall satisfaction rated ‘excellent’ or ‘good’ was seen in 87% of responses) but also identified areas of improvement, such as in managing postprocedure pain and having a separate space for adolescents for preprocedure discussions. Improvements in satisfaction scores were noted in one unit over time, particularly in preprocedure preparation (from 86% to 100%), and overall satisfaction with endoscopy experience (81%–100%).

Conclusion

All three paediatric endoscopy services found this questionnaire useful in identifying areas needing improvement and in demonstrating compliance with measures within the P-GRS quality of patient experience domain. Further work includes exploring ways to increase response rates, as well as developing age-appropriate and electronic versions.
Patient experience of gastrointestinal endoscopy: informing the development of the Newcastle ENDOPREM™
Authors: Neilson Laura J , Patterson Joanne , von Wagner Christian , Hewitson Paul , McGregor Lesley M , Sharp Linda , Rees Colin J
Published: January 2020

Background

Measuring patient experience is important for evaluating the quality of patient care, identifying aspects requiring improvement and optimising patient outcomes. Patient Reported Experience Measures (PREMs) should, ideally, be patient derived, however no such PREMs for gastrointestinal (GI) endoscopy exist. This study explored the experiences of patients undergoing GI endoscopy and CT colonography (CTC) in order to: identify aspects of care important to them; determine whether the same themes are relevant across investigative modalities; develop the framework for a GI endoscopy PREM.

Methods

Patients aged ≥18 years who had undergone oesophagogastroduodenoscopy (OGD), colonoscopy or CTC for symptoms or surveillance (but not within the national bowel cancer screening programme) in one hospital were invited to participate in semi-structured interviews. Recruitment continued until data saturation. Inductive thematic analysis was undertaken.

Results

35 patients were interviewed (15 OGD, 10 colonoscopy, 10 CTC). Most patients described their experience chronologically, and five ‘procedural stages’ were evident: before attending for the test; preparing for the test; at the hospital, before the test; during the test; after the test. Six themes were identified: anxiety; expectations; choice & control; communication & information; comfort; embarrassment & dignity. These were present for all three procedures but not all procedure stages. Some themes were inter-related (eg, expectations & anxiety; communication & anxiety).

Conclusion

We identified six key themes encapsulating patient experience of GI procedures and these themes were evident for all procedures and across multiple procedure stages. These findings will be used to inform the development of the Newcastle ENDOPREM™.
The clinical relevance of intragenic NRXN1 deletions
Authors: Cosemans Nele , Vandenhove Laura , Vogels Annick , Devriendt Koenraad , Van Esch Hilde , Van Buggenhout Griet , Olivié Hilde , de Ravel Thomy , Ortibus Els , Legius Eric , Aerssens Peter , Breckpot Jeroen , R. Vermeesch Joris , Shen Sanbing , Fitzgerald Jacqueline , Gallagher Louise , Peeters Hilde
Published: January 2020

Background

Intragenic NRXN1 deletions are susceptibility variants for neurodevelopmental disorders; however, their clinical interpretation is often unclear. Therefore, a literature study and an analysis of 43 previously unpublished deletions are provided.

Methods

The literature cohort covered 629 heterozygous NRXN1 deletions: 148 in controls, 341 in probands and 140 in carrier relatives, and was used for clinical hypothesis testing. Exact breakpoint determination was performed for 43 in-house deletions.

Results

The prevalence of exonic NRXN1 deletions in controls was ~1/3000 as compared with ~1/800 in patients with neurodevelopmental/neuropsychiatric disorders. The differential distribution of deletions across the gene between controls and probands allowed to distinguish distinct areas within the gene. Exon 6–24 deletions appeared only twice in over 100000 control individuals, had an estimated penetrance for neurodevelopmental disorders of 32.43%, a de novo rate of 50% and segregated mainly with intellectual disability (ID) and schizophrenia. In contrast, exon 1–5 deletions appeared in 20 control individuals, had an estimated penetrance of 12.59%, a de novo rate of 32.5% and were reported with a broad range of neurodevelopmental phenotypes. Exact breakpoint determination revealed six recurrent intron 5 deletions.

Conclusion

Exon 6–24 deletions have a high penetrance and are mainly associated with ID and schizophrenia. In contrast, the actual contribution of exon 1–5 deletions to a neurodevelopmental/neuropsychiatric disorder in an individual patient and family remains very difficult to assess. To enhance the clinical interpretation, this study provides practical considerations for counselling and an interactive table for comparing a deletion of interest with the available literature data.
Normal-range emergency department serum phosphorus levels and all-cause mortality
Authors: Barash Yiftach , Klang Eyal , Soffer Shelly , Zimlichman Eyal , Leibowitz Avshalom , Grossman Ehud , Shlomai Gadi
Published: January 2020

Purpose of the study

Hypophosphataemia and hyperphosphataemia are frequently encountered in hospitalised patients and are associated with significant clinical consequences. However, the prognostic value of normal-range phosphorus levels on all-cause mortality and hospitalisations is not well established. Therefore, we examined the association between normal-range phosphorus levels, all-cause mortality and hospitalisations in patients presenting to the emergency department of a tertiary medical centre in Israel.

Study design

A retrospective analysis of patients presenting to the Chaim Sheba Medical Center emergency department between 2012 and 2018. The cohort was divided into quartiles based on emergency department phosphorus levels: ‘very-low-normal’ (p ≥ 2 mg/dL and p ≤ 2.49 mg/dL), ‘low-normal’ (p ≥ 2.5 mg/dL and p ≤ 2.99 mg/dL), ‘high-normal’ (p≥  3 mg/dL and p≤3.49 mg/dL) and ‘very-high-normal’ (p ≥  3.5 mg/dL and p ≤ 4 mg/dL). We analysed the association between emergency department phosphorus levels, hospitalisation rate and 30-day and 90-day all-cause mortality.

Results

Our final analysis included 223 854 patients with normal-range phosphorus levels. Patients with ‘very-low-normal’ phosphorus levels had the highest mortality rate. Compared with patients with ‘high-normal’ phosphorus levels, patients with ‘very-low-normal’ levels had increased 30-day all-cause mortality (OR 1.3, 95% CI 1.1 to 1.4, p<0.001), and increased 90-day all-cause mortality (OR 1.2, 95% CI 1.1 to 1.3, p<0.001). Lower serum phosphorus levels were also associated with a higher hospitalisation rate, both for the internal medicine and general surgery wards (p<0.001).

Conclusions

Lower phosphorus levels, within the normal range, are associated with higher 30-day and 90-day all-cause mortality and hospitalisation rate.
Choice of spinal cord stimulation versus targeted drug delivery in the management of chronic pain: a predictive formula for outcomes
Authors: Mekhail Nagy , Mehanny Diana S , Armanyous Sherif , Costandi Shrif , Saweris Youssef , Azer Gerges , Bolash Robert
Published: January 2020

Contemporary nonmalignant pain treatment algorithms commence with conservative non-invasive strategies, later progressing from minimally invasive interventions to invasive techniques or implantable devices. The most commonly used implantable devices are spinal cord stimulation (SCS) systems or targeted drug delivery (TDD) devices. Historically, SCS had been considered in advance of TDD, positioning TDD behind SCS failures. Following Institutional Review Board approval, data were extracted from electronic medical records of patients who underwent SCS trial in the Department of Pain Management at Cleveland Clinic from 1994 to 2013. The sample size was analyzed in two cohorts: those who succeeded with SCS and those who failed SCS and consequently proceeded to TDD. Univariate and multivariate analyses were performed and a predictive formula for successful outcomes was created. 945 patients were included in the cohort of which 119 (12.6%) subjects achieved adequate pain relief with TDD after failure of SCS. Gender, age, depression and primary pain diagnosis were significantly different in this subgroup. Males were 52% less likely to experience pain relief with SCS. The odds of SCS success decreased as age increased by 6% per year. Patients with comorbid depression, interestingly, were 63% more likely to succeed with SCS. A logistic model was created to predict SCS success which was used to create a predictive formula. Older male patients diagnosed with spine-related pain were more likely to benefit from TDD than SCS. This observation potentially identifies a subgroup in whom consideration for TDD in advance of SCS failure could prove more efficient and cost effective. These retrospective findings warrant prospective comparative studies to validate this derived predictive formula.
Association of the addition of a transversus abdominis plane block to an enhanced recovery program with opioid consumption, postoperative antiemetic use, and discharge time in patients undergoing laparoscopic bariatric surgery: a retrospective study
Authors: McCarthy Robert J , Ivankovich Katarina G , Ramirez Emily A , Adams Ashley M , Ramesh Arjun K , Omotosho Philip A , Buvanendran Asokumar
Published: January 2020

Background

Increasing numbers of laparoscopic bariatric surgeries are being performed and enhanced recovery from anesthesia and surgery (ERAS) protocols have been implemented to optimize care for these patients. We evaluated the effects of an anesthesiologist placed preoperative transversus abdominis plane block (TAP) as part of a bariatric surgery ERAS protocol. We hypothesized that an anesthesiologist placed preoperative TAP added to an ERAS protocol following laparoscopic bariatric surgery would reduce total opioid consumption.

Methods

A retrospective cohort of consecutive patients between January 1, 2017 and December 31, 2018 at a single large tertiary care center studied. TAP blocks were added to the ERAS protocol beginning in the second quarter of 2017. The primary outcome was total opioid analgesia use in mg oral morphine equivalents. Secondary outcomes were antiemetics administered and length of hospitalization. Data were analyzed using a generalized linear mixed model adjusted for sociodemographic, surgical, and preoperative risk factors that have been associated with opioid and antiemetic use and length of hospitalization.

Results

Five hundred and nine cases were analyzed; TAP blocks were performed in 94/144 (65%) laparoscopic Roux-en-Y gastric bypass (LRYGB) and in 172/365 (47%) laparoscopic sleeve gastrectomy (LSG) patients. Mean (95% CI) adjusted total opioid administered was lower by 11% (1% to 19%, p=0.02), antiemetic drug administration was lower by 15% (-2% to 25%, p=0.06) and discharge time lower by 39% (26% to 48%, p<0.01) following LRYGB in the TAP group. Mean (95% CI) adjusted total opioid administered was lower by 9% (2% to 16%, p<0.01), antiemetic drug administration was lower by 11% (3% to 18%, p<0.01) and discharge time lower by 11% (2% to 18%, p=0.02) following LSG in the TAP group.

Conclusions

TAP blocks added to a laparoscopic bariatric surgery ERAS protocol were associated with decreased total opioid use, number of antiemetic treatments, and length of stay; however, these changes were not likely clinically important. Our findings do not support widespread clinical benefit of TAP use in ERAS protocols for laparoscopic bariatric surgery.
Cigarette and cigar sales in Hawaii before and after implementation of a Tobacco 21 Law
Authors: Glover-Kudon Rebecca , Gammon Doris G , Rogers Todd , Coats Ellen M , Loomis Brett , Johnson Lila , Welton MaryBeth , Lavinghouze René
Published: January 2020

Introduction

On 1 January 2016, Hawaii raised the minimum legal age for tobacco access from 18 to 21 years (‘Tobacco 21 (T21)’) statewide, with no special population exemptions. We assessed the impact of Hawaii’s T21 policy on sales of cigarettes and large cigars/cigarillos in civilian food stores, including menthol/flavoured product sales share.

Methods

Cigarette and large cigar/cigarillo sales and menthol/flavoured sales share were assessed in Hawaii, California (implemented T21 in June 2016 with a military exemption), and the US mainland using the only Nielsen data consistently available for each geographical area. Approximate monthly sales data from large-scale food stores with sales greater than US$2 million/year covered June 2012 to February 2017. Segmented regression analyses estimated changes in sales from prepolicy to postpolicy implementation periods.

Results

Following T21 in Hawaii, average monthly cigarette unit sales dropped significantly (−4.4%, p<0.01) coupled with a significant decrease in menthol market share (−0.8, p<0.01). This combination of effects was not observed in comparison areas. Unit sales of large cigars/cigarillos decreased significantly in each region following T21 implementation. T21 policies in Hawaii and California showed no association with flavoured/menthol cigar sales share, but there was a significant increase in flavoured/menthol cigar sales share in the USA (7.1%, p<0.01) relative to Hawaii’s implementation date, suggesting T21 may have attenuated an otherwise upward trend.

Conclusions

As part of a comprehensive approach to prevent or delay tobacco use initiation, T21 laws may help to reduce sales of cigarette and large cigar products most preferred by US youth and young adults.
Construction and resource short-term planning using a BIM-based ontological decision support system
Authors: Tavakolan Mehdi , Mohammadi Sina , Zahraie Banafsheh
Published: January 2020

The dynamic nature and increasing complexity of the construction projects impose many challenges for project planning and control. As a project progresses, more information becomes available and the level of uncertainty decreases. It can be used to proactively check the validity of the previous decisions and develop revised and more detailed plans for the upcoming activities in construction planning meetings. For this purpose, this study implements ontological knowledge representation and semantic reasoning techniques to propose an intelligent information collection and decision support system framework for short-term collaborative construction and resource planning. Moreover, a new approach is suggested that allows for incorporating resource specifications and limitations, and complex multi-factor constraints in the ontological planning process. The framework was tested based on a real-world construction project and different application cases were discussed. The framework showed a promising performance for analyzing different scenarios and help the planners making informative decisions.
Transcriptomic comparison of liver tissue between Anqing six-end-white pigs and Yorkshire pigs based on RNA sequencing
Authors: Wang Yuanlang , Zhang Wei , Wu Xudong , Wu Chaodong , Qian Li , Wang Li , Zhang Xiaodong , Yang Min , Li Dengtao , Ding Jian , Wang Chonglong , Yin Zongjun , Ding Yueyun
Published: January 2020

Chinese indigenous pig and Western commercial pig breeds show different patterns of lipid metabolism, fat deposition, and fatty acid composition; for these reasons, they have become vitally important models of energy metabolism and obesity in humans. To compare the mechanisms underlying lipid metabolism between Yorkshire pigs (lean type) and Anqing six-end-white pigs (obese type), the liver transcriptomes of six castrated boars with a body weight of approximately 100 kg (three Yorkshire and three Anqing) were analyzed by RNA-seq. The total number of reads produced for each liver sample ranged from 47.05 to 62.6 million. Among 362 differentially expressed genes, 142 were up-regulated and 220 were down-regulated in Anqing six-end-white pigs. Based on these data, 79 GO terms were significantly enriched. The top 10 (the 10 with lowest corrected P-value) significantly enriched GO terms were identified, including lipid metabolic process and carboxylic acid metabolic process. Pathway analysis revealed three significantly enriched KEGG pathways including PPAR signaling pathway, steroid hormone biosynthesis, and retinol metabolism. Based on protein–protein interaction networks, multiple genes responsible for lipid metabolism were identified, such as PCK1, PPARA, and CYP7A1, and these were considered promising candidate genes that could affect porcine liver lipid metabolism and fat deposition. Our results provide abundant transcriptomic information that will be useful for animal breeding and biomedical research.
Laser-wakefield application to oncology
Authors: Nicks B. S. , Tajima T. , Roa D. , Nečas A. , Mourou G.
Published: January 2020

Recent developments in fiber lasers and nanomaterials have allowed the possibility of using laser wakefield acceleration (LWFA) as the source of low-energy electron radiation for endoscopic and intraoperative brachytherapy, a technique in which sources of radiation for cancer treatment are brought directly to the affected tissues, avoiding collateral damage to intervening tissues. To this end, the electron dynamics of LWFA is examined in the high-density regime. In the near-critical density regime, electrons are accelerated by the ponderomotive force followed by an electron sheath formation, resulting in a flow of bulk electrons. These low-energy electrons penetrate tissue to depths typically less than 1 mm. First a typical resonant laser pulse is used, followed by lower-intensity, longer-pulse schemes, which are more amenable to a fiber-laser application.
Traffic assignment model for combined mode with travel condition constraints
Authors: Yu Xiaohua , Wang Hua , Ge Zhenzhen , Guo Jianmin
Published: January 2020

Combined-mode traffic assignment is one of the key links for multi-modal transportation planning. In order to quantitatively evaluate the implementation effect of combined-mode transportation and explore its assignment mechanism, a combined-mode traffic assignment model with travel constraints is proposed. First, the practical factors of combined mode in real world are discussed and integrated into the analysis of multi-modal network transformation as related constraints. Second, the physical transportation network is translated to equivalent super network (SN) and state-augmented network (SAN) based on the graph theory. Moreover, the network size constrained by the actual conditions is conducive to further analysis of combined-mode trips. Third, a tri-level combined-mode traffic assignment model is formulated based on the simulation platform of SAN. The first level of the model is to address the combined-mode choice, the second level is to transfer choice on SAN, and the third level is to characterize auto travelers’ route choice behavior. By analyzing the impedance in multi-level network, an MSA algorithm solving Nest-Logit model is proposed. Finally, numerical example is performed to validate the model. The method proposed in this paper considers the travel similarity, reduces the network scale, conforms to the travel logic and makes up for the shortcomings of traditional traffic allocation methods.
Search for exotic features in the ground state light nuclei with 10 ≤Z ≤ 18 from stable valley to drip lines
Authors: Saxena G. , Kumawat M. , Aggarwal Mamta
Published: January 2020

We present a systematic description of the exotic features in the ground states of light nuclei from the stable valley to the drip lines. A study with the even and odd isotopes of Ne, Mg, Si, S and Ar has been performed using theoretical formalisms (i) Relativistic mean-field plus state-dependent BCS approach and (ii) Macroscopic–Microscopic (MM) approach using the triaxially deformed Nilsson–Strutinsky Method. The computed binding energies and one- and two-neutron separation energies using both the theories show magic character of [Formula: see text] and 40. The neutron and proton radii and the neutron densities show a well-developed neutron skin in the neutron-rich isotopes. The exotic phenomena such as weakly bound structures and the central density depletion characterized as bubble effect are explored. Our calculations for the single particle levels, density profiles and the charge form factors indicate bubble-like structures. Few new candidates of bubble nuclei are identified. Most of the nuclei in this region are found deformed with mostly prolate shape and few triaxial shapes while many nuclei exhibit the phenomenon of shape coexistence. Our results display a reasonable agreement between both the theories and the available experimental data.
Decentralized Incremental Fuzzy Reinforcement Learning for Multi-Agent Systems
Authors: Hamzeloo Sam , Jahromi Mansoor Zolghadri
Published: January 2020

We present a new incremental fuzzy reinforcement learning algorithm to find a sub-optimal policy for infinite-horizon Decentralized Partially Observable Markov Decision Processes (Dec-POMDPs). The algorithm addresses the high computational complexity of solving large Dec-POMDPs by generating a compact fuzzy rule-base for each agent. In our method, each agent uses its own fuzzy rule-base to make the decisions. The fuzzy rules in these rule-bases are incrementally created and tuned according to experiences of the agents. Reinforcement learning is used to tune the behavior of each agent in such a way that maximum global reward is achieved. In addition, we propose a method to construct the initial rule-base for each agent using the solution of the underlying MDP. This drastically improves the performance of the algorithm in comparison with random initialization of the rule-base. We assess the performance of our proposed method using several benchmark problems in comparison with some state-of-the-art methods. Experimental results show that our algorithm achieves better or similar reward when compared with other methods. However, from the runtime point of view, our method is superior to all previous methods. Using a compact fuzzy rule-base not only decreases the amount of memory used but also significantly speeds up the learning phase.
Developing Cognitive and Non-Cognitive Entrepreneurial Competences through Business Simulation Games
Authors: Costin Yvonne , O’Brien Michael P. , Hynes Briga
Published: January 2020

Today, entrepreneurship is seen as a major driver for innovation, economic growth and job creation, with entrepreneurial competencies highly sought after by practitioners and policy-makers alike. Competencies considered entrepreneurial include knowledge about how entrepreneurs create value; skills in marketing, resource acquisition and opportunity identification; and attitudes such as entrepreneurial passion, self-efficacy, proactiveness and tenacity. There is widespread consensus in the literature that entrepreneurial competencies can be developed through entrepreneurship learning. This study adopts an existing framework for entrepreneurial competencies based on previous research to investigate the role and influence that simulation games can play in the development of cognitive (knowledge and skills) and non-cognitive (attitudes) entrepreneurial competencies. The paper showcases the many benefits of using business simulation as an effective mode for developing entrepreneurial competencies. Such competencies are not only beneficial for individuals working in an entrepreneurial context — but are transferable to any business context, bringing to the fore the importance of entrepreneurial learning for all students to develop such competencies.
Noncommutative G-hereditary rings
Authors: Li Yunxia , Wang Jian , Geng Yuxian , Hu Jiangsheng
Published: January 2020

In this paper, we introduce and study left (right) [Formula: see text]-hereditary rings over any associative ring, and these rings are exactly [Formula: see text]-hereditary rings defined by Mahdou and Tamekkante provided that [Formula: see text] is a commutative ring. As applications, we give a partial answer to the question posed by Bazzoni, Cort[Formula: see text]s-Izurdiaga and Estrada, and characterize when the character module of a Gorenstein injective left [Formula: see text]-module is Gorenstein flat provided that [Formula: see text] is a left [Formula: see text]-hereditary ring. In addition, some new characterizations of left hereditary rings are given.
Strong Gelfand pairs of symmetric groups
Authors: Anderson Gradin , Humphries Stephen P. , Nicholson Nathan
Published: January 2020

A strong Gelfand pair is a pair [Formula: see text], of finite groups such that the Schur ring determined by the [Formula: see text]-classes [Formula: see text], is a commutative ring. We find all strong Gelfand pairs [Formula: see text]. We also define an extra strong Gelfand pair [Formula: see text], this being a strong Gelfand pair of maximal dimension, and show that in this case [Formula: see text] must be abelian.