Publications by authors named "Robert Jones"

875 Publications

TRIM28 is a transcriptional activator of the mutant TERT promoter in human bladder cancer.

Proc Natl Acad Sci U S A 2021 Sep;118(38)

Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048;

Bladder cancer (BC) has a 70% telomerase reverse transcriptase (TERT or hTERT in humans) promoter mutation prevalence, commonly at -124 base pairs, and this is associated with increased hTERT expression and poor patient prognosis. We inserted a green fluorescent protein (GFP) tag in the mutant hTERT promoter allele to create BC cells expressing an hTERT-GFP fusion protein. These cells were used in a fluorescence-activated cell sorting-based pooled CRISPR-Cas9 Kinome knockout genetic screen to identify tripartite motif containing 28 (TRIM28) and TRIM24 as regulators of hTERT expression. TRIM28 activates, while TRIM24 suppresses, hTERT transcription from the mutated promoter allele. TRIM28 is recruited to the mutant promoter where it interacts with TRIM24, which inhibits its activity. Phosphorylation of TRIM28 through the mTOR complex 1 (mTORC1) releases it from TRIM24 and induces hTERT transcription. TRIM28 expression promotes in vitro and in vivo BC cell growth and stratifies BC patient outcome. mTORC1 inhibition with rapamycin analog Ridaforolimus suppresses TRIM28 phosphorylation, hTERT expression, and cell viability. This study may lead to hTERT-directed cancer therapies with reduced effects on normal progenitor cells.
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http://dx.doi.org/10.1073/pnas.2102423118DOI Listing
September 2021

Reduction in post-operative pancreatic fistula with polyethylene glycol and recombinant human albumin sealant following stapled distal pancreatectomy.

ANZ J Surg 2021 Sep 13. Epub 2021 Sep 13.

The University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia.

Background: Postoperative pancreatic fistula (POPF) remains a significant cause of morbidity in patients undergoing distal pancreatectomy (DP). The use of polyethylene glycol (PEG) and recombinant human albumin sealant gel applied to the transected pancreatic margin in DP may reduce POPF rates and was assessed.

Methods: A retrospective single centre cohort study of patient undergoing DP at an Australian high volume tertiary institution between January 2015 and January 2021. Rates of POPF in patients undergoing stapled pancreatic transection with PEG sealant were compared to other methods.

Results: A total of 54 cases were identified for analysis, with 16 undergoing stapled DP combined with staple line application of PEG (PEG group). Most patients in the control group had stapled DP 92% (35 of 38), with 47% (18 of 38) combined with a reinforcing buttress, with or without the use other glue types. Overall, 28 of 54 (52%) developed a POPF, with a significantly lower rate in the PEG group (3 of 16 vs. 25 of 38 in the Control group; p = 0.003). Clinically significant Grade B/C POPF was lower in the PEG group (0 of 16 vs. 9 of 28 in the Control group; p = 0.045), and patients in the PEG group had a shorter median (range) length of hospital stay (6 [4-14] days vs. 10 [6-41] days p = 0.04).

Conclusion: Stapled DP with the application of PEG and recombinant human albumin sealant to the transection line appears to be associated with a lower rate of clinically significant POPF.
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http://dx.doi.org/10.1111/ans.17181DOI Listing
September 2021

Do clinical trials change practice? A longitudinal, international assessment of colorectal cancer prescribing practices.

Cancer Treat Res Commun 2021 17;28:100445. Epub 2021 Aug 17.

Beatson West of Scotland Cancer Centre and Institute of Cancer Sciences, University of Glasgow 1053 Great Western Road, G12 0YN Wolfson Wohl Cancer Research Centre, Glasgow, United Kingdom.

Introduction: Over half of the 1.5 million individuals globally who are diagnosed with colorectal cancer (CRC) present with stage II-III disease. Understanding clinician attitudes towards treatment for this group is paramount to contextualise real-world outcomes and plan future trials. The aim of this study was to assess clinician awareness of trials assessing the optimal duration of CRC adjuvant therapy, their attitudes towards shorter treatment and their self-reported practice.

Methods: A survey was developed using OnlineSurveys® and distributed to clinicians in April 2019, with a follow-up survey disseminated to a subset of respondents in August 2020. Microsoft Excel® and Stata® were used for analysis.

Results: 265 clinicians replied to the first survey, with the majority aware of findings from the International Duration Evaluation of Adjuvant Therapy collaboration and contributory trials. Practice change was greatest for patients under 70 with low-risk stage III CRC, with most uncertainty around using 3-months of doublet chemotherapy for high-risk stage II disease. In August 2020, clinicians (n = 106) were more likely to use 3-months of FOLFOX for low-risk stage III disease and 3-months of CAPOX for stage II disease compared to April 2019. There was no indication that the COVID-19 pandemic had enduring changes on treatment decisions beyond those made in response to trial evidence.

Discussion: Clinicians use a risk-stratified approach to treat CRC the adjuvant setting. Lower utilisation of doublet chemotherapy for older and stage II patients has affected the extent of trial implementation. Active dialogue regarding how trial results apply to these groups may improve consensus.
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http://dx.doi.org/10.1016/j.ctarc.2021.100445DOI Listing
September 2021

Elevated levels of circulating mitochondrial DNA predict early allograft dysfunction in patients following liver transplantation.

J Gastroenterol Hepatol 2021 Aug 23. Epub 2021 Aug 23.

Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.

Background And Aim: The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study.

Methods: Twenty-one patients were enrolled prospectively prior to LT.

Results: Postoperative complications were observed in 47.6% (n = 10). Seven patients (33.3%) had early allograft dysfunction (EAD), and six patients (28.5%) experienced acute cellular rejection within 6 months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1 361 937 copies/mL [IQR 586 781-3 399 687] after LT; 545 531 copies/mL [IQR 238 562-1 381 015] before LT; and 194 562 copies/mL [IQR 182 359-231 515] in healthy controls) and returned to normal levels by 5 days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early postoperative period (P < 0.001). In all patients, there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (P < 0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at postoperative day 7, which did not correlate with liver function tests.

Conclusions: The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests.
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http://dx.doi.org/10.1111/jgh.15670DOI Listing
August 2021

Urine strontium-90 (Sr-90) manual and automated pre-analytical separation followed by liquid scintillation counting.

J Radioanal Nucl Chem 2021 ;329(1):383-390

Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Inorganic and Radiation Analytical Toxicology Branch, 4770 Buford Hwy, MS S-110-5, Atlanta, GA 30341.

Responding to a radiological or nuclear incident may require assessing tens to hundreds of thousands of people for possible radionuclide contamination. The measurement of radioactive Sr is important because of its impact on people's health. The existing analytical method for urine Sr-90 analysis using crown ethers is laborious and involves possible exposure to concentrated acids; therefore, this work is devoted to the development of the automated Sr-90 separation process, which became possible with the prep pre-analytical system (Elemental Scientific, Inc).
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http://dx.doi.org/10.1007/s10967-021-07759-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371566PMC
January 2021

The effect of Sr resin cartridge age on stable Sr recovery methods used in Sr-90 analysis.

J Radioanal Nucl Chem 2021 Feb;328:369-375

Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Inorganic and Radiation Analytical Toxicology Branch, 4770 Buford Hwy, MS S110-5, Atlanta, GA 30341-3717.

Radioactive strontium is a nuclear fission decay product found in industrial products and nuclear waste and is released during nuclear accidents. Current urine radiostrontium separation methods often are based on the use of Sr resin columns or cartridges (Eichrom Technologies). Most of these analytical methods use stable Sr as a tracer, with subsequent Sr recovery. The gravimetric recovery method requires 120 times more stable Sr than does the inductively coupled plasma mass spectrometry method described here. This difference can affect cartridge performance especially with aging cartridges.
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http://dx.doi.org/10.1007/s10967-021-07628-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371671PMC
February 2021

Urine gross alpha/beta bioassay method development using liquid scintillation counting techniques.

J Radioanal Nucl Chem 2021 Jan;327(1):513-523

Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Inorganic and Radiation Analytical Toxicology Branch, 4770 Buford Hwy, MS S110-5, Atlanta, GA 30341-3717.

In the case of a radiological or nuclear incident, valuable information could be obtained in a timely manner by using Liquid Scintillation Counting (LSC) technique through fast screening of urine samples from potentially contaminated persons. This work describes the optimization of LSC parameters on PerkinElmer (PE) Tri-Carb and Quantulus GCT series instruments to develop a rapid method for screening urine in an emergency response situation.
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http://dx.doi.org/10.1007/s10967-020-07493-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371673PMC
January 2021

Universal use of alpha/beta mode in liquid scintillation counting analysis for both alpha/beta and single nuclide determination.

J Radioanal Nucl Chem 2021 Jan;327:975-983

Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Inorganic and Radiation Analytical Toxicology Branch, 4770 Buford Hwy, MS S110-5, Atlanta, GA 30341-3717.

Nuclear industry advancements and growing concerns about environmental contamination and terrorist activity have increased interest in quantifying radioisotopes in environmental and human samples. Increased presence in the environment, ease of entry into the food chain, nuclear medicine applications, and the possibility of radiological terrorism incidents can lead to human intake of these radionuclides [1,2]. A universal method to screen for and quantify individual radionuclides as well as both levels of alpha and beta emitters would address these concerns.
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http://dx.doi.org/10.1007/s10967-020-07557-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371672PMC
January 2021

PhyloFisher: A phylogenomic package for resolving eukaryotic relationships.

PLoS Biol 2021 Aug 6;19(8):e3001365. Epub 2021 Aug 6.

Department of Biological Sciences, Mississippi State University, Mississippi State, Mississippi, United States of America.

Phylogenomic analyses of hundreds of protein-coding genes aimed at resolving phylogenetic relationships is now a common practice. However, no software currently exists that includes tools for dataset construction and subsequent analysis with diverse validation strategies to assess robustness. Furthermore, there are no publicly available high-quality curated databases designed to assess deep (>100 million years) relationships in the tree of eukaryotes. To address these issues, we developed an easy-to-use software package, PhyloFisher (https://github.com/TheBrownLab/PhyloFisher), written in Python 3. PhyloFisher includes a manually curated database of 240 protein-coding genes from 304 eukaryotic taxa covering known eukaryotic diversity, a novel tool for ortholog selection, and utilities that will perform diverse analyses required by state-of-the-art phylogenomic investigations. Through phylogenetic reconstructions of the tree of eukaryotes and of the Saccharomycetaceae clade of budding yeasts, we demonstrate the utility of the PhyloFisher workflow and the provided starting database to address phylogenetic questions across a large range of evolutionary time points for diverse groups of organisms. We also demonstrate that undetected paralogy can remain in phylogenomic "single-copy orthogroup" datasets constructed using widely accepted methods such as all vs. all BLAST searches followed by Markov Cluster Algorithm (MCL) clustering and application of automated tree pruning algorithms. Finally, we show how the PhyloFisher workflow helps detect inadvertent paralog inclusions, allowing the user to make more informed decisions regarding orthology assignments, leading to a more accurate final dataset.
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http://dx.doi.org/10.1371/journal.pbio.3001365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345874PMC
August 2021

Recovery and Its Dynamics of Filamentous Fungi from Clinical Specimen Cultures: An Extensive Study.

Microbiol Spectr 2021 Sep 4;9(1):e0008021. Epub 2021 Aug 4.

Quest Diagnostics Nichols Institute, Chantilly, Virginia, USA.

The culture method remains vital in diagnosing fungal infections, but extensive data-based evaluation of the method, especially for filamentous fungi (molds), is minimal. The purpose of this study was to characterize mold recoveries from fungal cultures and the impact of media and incubation duration. Clinical specimens for fungal cultures were submitted primarily from the eastern and central United States, and mold isolation data were prospectively collected and analyzed. A total of 1,821 molds in 59 genera were isolated from 1,687 positive specimens, accounting for approximately 5.6% of our cohort of 30,000 fungal cultures. Within 2 weeks, nearly 90% of molds and 97.3% of Aspergillus fumigatus complex were recovered (>95% confidence interval [CI]). All fungi were recovered within 11 days of incubation. The recovery peak time was day 3 for fungi, day 4 for hyaline molds, day 5 for dematiaceous molds, and day 7 for fungi. The recovery of Histoplasma capsulatum and species in the fourth week of incubation reveals that a 3-week incubation time is insufficient. Inhibitory mold agar was the best medium for recovering all mold types among all tested specimen types, yielding nearly 78% of mold growth overall, indicating the necessity of selective medium for fungal cultures. Fungal culture is the gold standard method of diagnosing fungal infections, but important information, such as the impact of media and incubation times on fungal recovery, is not well documented. This study addressed these gaps using extensive data-based evaluation focused on molds. We identified the best medium types and incubation times for better fungal culture practice. We analyzed 1,821 molds from 1,687 positive specimens in our cohort of approximately 30,000 fungal cultures. Mold recovery peaked between 3 and 7 days of incubation, dependent upon the type of mold. Some well-defined fungal pathogens, such as Histoplasma capsulatum and species, were isolated in the fourth week of incubation. Inhibitory mold agar was identified as the best medium for recovering all mold types among all tested specimen sources. As we are aware, this is the largest study of fungal culture methods and supports 4 weeks of incubation for optimal mold recovery.
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http://dx.doi.org/10.1128/Spectrum.00080-21DOI Listing
September 2021

A Simple Reverse Transcriptase PCR Melting-Temperature Assay To Rapidly Screen for Widely Circulating SARS-CoV-2 Variants.

J Clin Microbiol 2021 09 21;59(10):e0084521. Epub 2021 Jul 21.

Public Health Research Institute, Center for Emerging Pathogens, Rutgers New Jersey Medical School, Newark, New Jersey, USA.

The increased transmission of SARS-CoV-2 variants of concern (VOC), which originated in the United Kingdom (B.1.1.7/alpha), South Africa (B1.351/beta), Brazil (P.1/gamma), the United States (B.1.427/429 or epsilon), and India (B.1.617.2/delta), requires a vigorous public health response, including real-time strain surveillance on a global scale. Although genome sequencing is the gold standard for identifying these VOCs, it is time-consuming and expensive. Here, we describe a simple, rapid, and high-throughput reverse transcriptase PCR (RT-PCR) melting-temperature () screening assay that identifies the first three major VOCs. RT-PCR primers and four sloppy molecular beacon (SMB) probes were designed to amplify and detect the SARS-CoV-2 N501Y (A23063T) and E484K (G23012A) mutations and their corresponding wild-type sequences. After RT-PCR, the VOCs were identified by a characteristic of each SMB. Assay optimization and testing was performed with RNA from SARS-CoV-2 USA WA1/2020 (wild type [WT]), B.1.1.7, and B.1.351 variant strains. The assay was then validated using clinical samples. The limit of detection for both the WT and variants was 4 and 10 genomic copies/reaction for the 501- and 484-codon assays, respectively. The assay was 100% sensitive and 100% specific for identifying the N501Y and E484K mutations in cultured virus and in clinical samples, as confirmed by Sanger sequencing. We have developed an RT-PCR melt screening test for the major VOCs that can be used to rapidly screen large numbers of patient samples, providing an early warning for the emergence of these variants and a simple way to track their spread.
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http://dx.doi.org/10.1128/JCM.00845-21DOI Listing
September 2021

NB-IoT Devices in Reverberation Chambers: A Comprehensive Uncertainty Analysis.

Int J Microw Wirel Technol 2021 Jul;13

Department of Electrical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands.

New protocols related to internet-of-things applications may introduce previously unnoticed measurement effects in reverberation chambers due to the narrowband nature of these protocols. Such technologies also require less loading to meet the coherence-bandwidth conditions, which may lead to higher variations, hence uncertainties, across the channel. In this work, we extend a previous study of uncertainty in NB-IoT and CAT-M1 device measurements in reverberation chambers by providing, for the first time, a comprehensive uncertainty analysis of the components related to the reference and DUT measurements. By use of a significance test, we show that certain components of uncertainty become more dominant for such narrowband protocols, and cannot be considered as negligible, as in current standardized test methods. We show that the uncertainty, if not accounted for by using the extended formulation, will be greatly overestimated and could lead to non-compliance to standards.
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http://dx.doi.org/10.1017/s1759078721000192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276118PMC
July 2021

Prospective observational study to examine health-related quality of life and develop models to predict long-term patient-reported outcomes 6 months after hospital discharge with blunt thoracic injuries.

BMJ Open 2021 07 8;11(7):e049292. Epub 2021 Jul 8.

Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King's College London, London, UK.

Objective: This study aimed to examine the long-term outcomes and health-related quality of life in patients with blunt thoracic injuries over 6 months from hospital discharge and develop models to predict long-term patient-reported outcomes.

Design: A prospective observational study using longitudinal survey design.

Setting: The study recruitment was undertaken at 12 UK hospitals which represented diverse geographical locations and covered urban, suburban and rural areas across England and Wales.

Participants: 337 patients admitted to hospital with blunt thoracic injuries were recruited between June 2018-October 2020.

Methods: Participants completed a bank of two quality of life surveys (Short Form-12 (SF-12) and EuroQol 5-Dimensions 5-Levels) and two pain questionnaires (Brief Pain Inventory and painDETECT Questionnaire) at four time points over the first 6 months after discharge from hospital. A total of 211 (63%) participants completed the outcomes data at 6 months after hospital discharge.

Outcomes Measures: Three outcomes were measured using pre-existing and validated patient-reported outcome measures. Outcomes included: Poor physical function (SF-12 Physical Component Score); chronic pain (Brief Pain Inventory Pain Severity Score); and neuropathic pain (painDETECT Questionnaire).

Results: Despite a trend towards improving physical functional and pain at 6 months, outcomes did not return to participants perceived baseline level of function. At 6 months after hospital discharge, 37% (n=77) of participants reported poor physical function; 36.5% (n=77) reported a chronic pain state; and 22% (n=47) reported pain with a neuropathic component. Predictive models were developed for each outcome highlighting important data collection requirements for predicting long-term outcomes in this population. Model diagnostics including calibration and discrimination statistics suggested good model fit in this development cohort.

Conclusions: This study identified the recovery trajectories for patients with blunt thoracic injuries over the first 6 months after hospital discharge and present prognostic models for three important outcomes which after external validation could be used as clinical risk stratification scores.
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http://dx.doi.org/10.1136/bmjopen-2021-049292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268921PMC
July 2021

Public health messages on arboviruses transmitted by Aedes aegypti in Brazil.

BMC Public Health 2021 07 9;21(1):1362. Epub 2021 Jul 9.

Department of Epidemiology and Global Health, Faculty of Medicine, Umeå University, Umeå, Sweden.

Background: The outbreak of Zika virus in Brazil in 2015 followed the arrival of chikungunya in 2014 and a long history of dengue circulation. Vital to the response to these outbreaks of mosquito-borne pathogens has been the dissemination of public health messages, including those promoted through risk communication posters. This study explores the content of a sample of posters circulated in Brazil towards the end of the Zika epidemic in 2017 and analyses their potential effectiveness in inducing behaviour change.

Methods: A content analysis was performed on 37 posters produced in Brazil to address outbreaks of mosquito-borne pathogens. The six variables of the Health Belief Model were used to assess the potential effectiveness of the posters to induce behaviour change.

Results: Three overarching key messages emerged from the posters. These included (i) the arboviruses and their outcomes, (ii) a battle against the mosquito, and (iii) a responsibility to protect and prevent. Among the six variables utilised through the Health Belief Model, cues to action were most commonly featured, whilst the perceived benefits of engaging in behaviours to prevent arbovirus transmission were the least commonly featured.

Conclusions: The posters largely focused on mosquito-borne transmission and the need to eliminate breeding sites, and neglected the risk of the sexual and congenital transmission of Zika and the importance of alternative preventive actions. This, we argue, may have limited the potential effectiveness of these posters to induce behaviour change.
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http://dx.doi.org/10.1186/s12889-021-11339-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272386PMC
July 2021

The use of organ donor blood in liver transplantation.

Clin Transplant 2021 Jul 8. Epub 2021 Jul 8.

Victorian Liver Transplant Unit, Austin Health, Melbourne, Australia.

Background: Blood removed from organs during deceased donor organ procurement is routinely discarded but is a potential resource for donor-specific transfusion (DST) in subsequent liver transplantation (LT). This study retrospectively analyses the impact of DST on intraoperative bank blood product usage, long-term graft, and patient survival, as well as frequency of rejection post-LT.

Methods: A total of 992 adult LT performed from 1993 to 2018 in a single quaternary center were included. Intraoperative blood product usage, patient, and graft survival, as well as acute and chronic rejection were assessed in patients who received blood retrieved from the organ donor, the "donor blood" (DB) group (n = 437) and patients who did not, the "no donor blood" (NDB) group (n = 555).

Results: Processing of DB ensured safe levels of potassium, magnesium, and insulin. There were fewer units of bank red blood cells transfusion required in the DB group compared to NDB group (2 vs. 4 units, P = .01). Graft survival was significantly superior in the DB group (10-year survival 75% vs. 69%, respectively, P = .04) but DST was not an independent predictor of graft survival. There was no significant difference in patient survival or rejection between the groups. There was no difference in treated, biopsy-proven rejection between the two groups.

Conclusions: This is the first large-cohort study assessing long-term outcomes of intraoperative DST in LT. The collection of organ donor blood and subsequent use in LT recipients appeared feasible with appropriate quality checks ensuring safety. DST resulted in a reduction in the use of packed red blood cells. There was no difference in the rate of rejection or graft or patient survival.
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http://dx.doi.org/10.1111/ctr.14419DOI Listing
July 2021

A UK Expert Consensus Approach for Managing Symptomatic Arteriovenous Fistula (AVF) Stenosis in Haemodialysis Patients.

Cardiovasc Intervent Radiol 2021 Jul 6. Epub 2021 Jul 6.

King's College Hospital NHS Foundation Trust, London, UK.

Purpose: Stenoses in mature arteriovenous fistulas (AVFs) are common and can negatively impact on the quality of haemodialysis, the longevity of the AVF and lead to debilitating symptoms. Multiple treatment options exist; however, management can vary between different centres. We aimed to establish multidisciplinary consensus on the optimal stepwise application of interventions based on evidence and consensus.

Methods: A modified Delphi process was conducted with 13 participants from hospitals across the UK, all of whom have high-volume dialysis access practice.

Results: The usual intervention to rectify de novo stenoses of mature AVFs is fistuloplasty, although surgery for inflow segment stenoses is also clinically acceptable. Appropriate first-line interventions include plain old balloon angioplasty or high-pressure balloon angioplasty; if these fail during the fistuloplasty, consider upsizing the balloon, prolonged balloon inflation or using alternative interventions, such as cutting or scoring balloons and ultra-high-pressure balloons. Alternative or subsequent interventions vary by anatomical site and may require additional multidisciplinary team input. For a stenoses recurring between 3 and 12 months, it is appropriate to consider interventions used de novo, but with a lower threshold for using drug-coated balloons (DCBs) in all regions and for using stent grafts in all regions but inflow segment. Recurrence after 12 months should be treated as a de novo lesion, with DCBs considered if they have been used successfully during previous interventions.

Conclusions: These recommendations aim to provide a practical guide to multidisciplinary teams in order to optimise the use of multiple interventions for rectifying AVF stenoses and provide unified evidence-based practice guidelines.
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http://dx.doi.org/10.1007/s00270-021-02875-5DOI Listing
July 2021

Anti-PF4 testing for vaccine-induced immune thrombocytopenia and thrombosis and heparin induced thrombocytopenia: Results from a UK National External Quality Assessment Scheme exercise April 2021.

J Thromb Haemost 2021 09 5;19(9):2263-2267. Epub 2021 Jul 5.

UK NEQAS (Blood Coagulation), Sheffield, UK.

Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the administration of the AstraZeneca (AZ) ChAdOx1 nCOV-19 vaccine has recently been reported. The associated clinical and laboratory features have included thrombosis at unusual sites, thrombocytopenia, and raised D-dimers with positivity for IgG anti-platelet factor 4 (PF4) antibodies.

Objectives: A UK National External Quality Control Assessment Scheme external quality control exercise was carried out by distributing liquid and lyophilized samples from a subject with VITT, a pool of samples from subjects with classical heparin-induced thrombocytopenia (HIT), and a non-VITT/non-HIT case to 85 centers performing HIT testing.

Methods: Participating centers employed their locally validated testing methods for HIT assays.

Results: The lyophilized and liquid samples were found to be commutable for the ELISA assays used in the detection of anti-PF4 antibodies. The Aeskulisa, Stago, Hyphen, and LIFECODES anti-PF4 ELISA assays successfully detected the VITT antibody, whereas the Acustar HIT, Werfen LIA, and the Stago STIC assays did not.

Conclusion: It is important that clinical and laboratory teams are aware of the limitations of some anti-PF4 assays when using them to aid diagnosis of VITT syndrome.
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http://dx.doi.org/10.1111/jth.15423DOI Listing
September 2021

Auscultation of Bowel Sounds and Ultrasound of Peristalsis Are Neither Compartmentalized Nor Correlated.

Cureus 2021 May 12;13(5):e14982. Epub 2021 May 12.

Emergency Medicine, MetroHealth Medical Center, Cleveland, USA.

Objective  Auscultation of bowel sounds has been taught as a component of the physical examination since the beginning of the 20th century. However, there has been little research or consensus on the significance of listening in different quadrants. Some textbooks indicate that bowel sounds are the result of peristalsis in that region, while others state that bowel sounds can be generalized over the entire abdominal wall. With ultrasonography, peristalsis can be visualized in a dynamic and non-invasive manner. The purpose of this study was to determine the relationship between auscultation of bowel sounds and visualization of peristalsis with ultrasound, to understand whether or not bowel sounds and peristalsis are compartmentalized. Methods Study participants quietly lay supine, while one investigator positioned an ultrasound probe on the abdomen visualizing the small intestine, and a second investigator placed an EKO Digital Stethoscope (Eko Devices, Inc., Oakland, CA) directly adjacent to the probe auscultate for bowel sounds. During a two-minute interval, a third investigator noted every time a bowel sound was heard (A+), peristalsis was seen (U+), or a combined event (C+) occurred, recording the total number of events. Measurements were recorded from four quadrants (right upper quadrant {RUQ}, left upper quadrant {LUQ}, right lower quadrant {RLQ}, left lower quadrant {LLQ}) and the periumbilical region (PUR). Fisher Exact test was used to determine whether there were significant differences between the number of bowel sounds heard but not seen (A+) and those seen but not heard (U+) with sounds that were both seen and heard (C+). Significance was determined with p < 0.05. Results  A total of 16 participants were included, with a combined 973 discrete bowel events, both auscultated and visualized. No quadrant showed a significant correlation between an isolated sound (A+) or peristalsis (U+) and a combined event (C+), indicating there were many events where an auscultated sound failed to correlate with observed peristalsis, and vice versa. The average p-value was 0.544, with a range of 0.052-1.00. Conclusion  This study showed that there is no significant correlation between auscultated bowel sounds and peristalsis within a given region. This study calls into question whether auscultation of all four quadrants provides more meaningful information than auscultation of one central point of the abdomen.
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http://dx.doi.org/10.7759/cureus.14982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202454PMC
May 2021

Rapid HPGe well detector gamma bioassay of Cs, Co, and Ir method.

Appl Radiat Isot 2021 Sep 11;175:109824. Epub 2021 Jun 11.

Inorganic and Radiation Analytical Toxicology Branch, Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop S103-1, Atlanta, GA, 30341, USA.

CDC designed a rapid HPGe Bioassay Method for Cs, Co, and Ir that is suitable for a public health response to a radiological incident where people may ingest or inhale radionuclides. The method uses a short count time, small sample volume, and a large volume detector and well size. It measures a patient's urine sample collected post-incident. The levels of concern are directly related to the Clinical Decision Guide levels recommended in the National Council of Radiation Protection 161.
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http://dx.doi.org/10.1016/j.apradiso.2021.109824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312759PMC
September 2021

Evaluating Uncertainty of Microwave Calibration Models With Regression Residuals.

IEEE Trans Microw Theory Tech 2020 Jun 8;68(6):2454-2467. Epub 2020 Apr 8.

National Institute of Standards and Technology, Boulder, CO 80305 USA.

We present a sensitivity-analysis and a Monte-Carlo algorithm for evaluating the uncertainty of multivariate microwave calibration models with regression residuals. We then use synthetic data to verify the performance of the algorithms and explore their limitations in the presence of correlated errors. The uncertainties we evaluate can be used to estimate the total uncertainty of a calibrated measurement when combined with the prediction intervals for that measurement.
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http://dx.doi.org/10.1109/tmtt.2020.2983358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194252PMC
June 2020

Perioperative chemotherapy versus surgery alone for resectable colorectal liver metastases: an international multicentre propensity score matched analysis on long-term outcomes according to established prognostic risk scores.

HPB (Oxford) 2021 May 15. Epub 2021 May 15.

HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain.

Background: There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence.

Methods: Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010-2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score.

Results: The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705-0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006).

Conclusion: Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.
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http://dx.doi.org/10.1016/j.hpb.2021.04.026DOI Listing
May 2021

Determination of Pu-239 in Urine by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS) Using an Automated Offline Sample Preparation Technique.

J Radioanal Nucl Chem 2021 Feb;328(1):277-287

Inorganic and Radiation Analytical Toxicology Branch, Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop S110-5, Atlanta, GA 30341, USA.

Here we report a new procedure to determine Pu-239 in urine using a custom-made automated pre-analytical processing system (single probe) with Pu-242 as a tracer followed by analysis by SF-ICP-MS. An average Pu-242 recovery rate of 88% was obtained with CF-ThU-1000 columns reused >100 times. Analytical results agree with measurements obtained using the CDC manual method with a R of 0.9994. Results for Oak Ridge National Laboratory (ORNL) reference materials (RM) align with target values with a bias range of -3.44% to 3.05%. The limit of detection for this method is 0.63 pg/L, which is comparable to previous manual methods.
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http://dx.doi.org/10.1007/s10967-021-07622-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176913PMC
February 2021

PET/CT Variants and Pitfalls in Breast Cancers.

Semin Nucl Med 2021 09 2;51(5):474-484. Epub 2021 Jun 2.

Department of Radiology, Division of Nuclear Medicine, Cleveland, Ohio; University Hospitals Cleveland Medical Center/Case Western Reserve University, Cleveland, Ohio. Electronic address:

There are a number of normal variants and pitfalls which are important to consider when evaluating F-18 Fluorodeoxyglucose (FDG) with Positron Emission Tomography (PET) in breast cancer patients. Although FDG-PET is not indicated for the initial diagnosis of breast cancer, focally increased glucose metabolism within breast tissue represents a high likelihood for a neoplastic process and requires further evaluation. Focally increased glucose metabolism is not unique to breast cancer. Other malignancies such as lymphoma, metastases from solid tumors as well as inflammatory changes also may demonstrate increased glucose metabolism either within the breast or at other sites throughout the body. Importantly, benign breast disease may also exhibit increased glucose metabolism, limiting the specificity of FDG-PET. Breast cancer has a wide range of metabolic activity attributed to tumor heterogeneity and breast cancer subtype. Intracellular signaling pathways regulating tumor glucose utilization contribute to these pitfalls of PET/CT in breast cancer. The evaluation of axillary lymph nodes by FDG-PET is less accurate than sentinel lymph node procedure, however is very accurate in identifying level II and III axillary lymph node metastases or retropectoral metastases. It is important to note that non-malignant inflammation in lymph nodes are often detected by modern PET/CT technology. Therefore, particular consideration should be given to recent vaccinations, particularly to COVID-19, which can commonly result in increased metabolic activity of axillary nodes. Whole body FDG-PET for staging of breast cancer requires specific attention to physiologic variants of FDG distribution and a careful comparison with co-registered anatomical imaging. The most important pitfalls are related to inflammatory changes including sarcoidosis, sarcoid like reactions, and other granulomatous diseases as well as secondary neoplastic processes.
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http://dx.doi.org/10.1053/j.semnuclmed.2021.04.005DOI Listing
September 2021

Point-of-care ultrasonography for the hospitalist.

Cleve Clin J Med 2021 06 2;88(6):345-359. Epub 2021 Jun 2.

Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.

Point-of-care ultrasonography (POCUS) has emerged as a vital tool in medicine. Initially used for procedural guidance, POCUS is now used for diagnostics and monitoring of the lung, heart, abdomen, and deep vein thrombosis. This wide applicability makes it an essential tool for hospitalists in daily clinical practice. This article provides an overview of the clinical integration of POCUS and basic image interpretation.
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http://dx.doi.org/10.3949/ccjm.88a.20141DOI Listing
June 2021

The integrin-mediated adhesive complex in the ancestor of animals, fungi, and amoebae.

Curr Biol 2021 Jul 1;31(14):3073-3085.e3. Epub 2021 Jun 1.

Department of Biological Sciences, Mississippi State University, Starkville, MS, USA; Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Starkville, MS, USA. Electronic address:

Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.
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http://dx.doi.org/10.1016/j.cub.2021.04.076DOI Listing
July 2021

Use of Patient Identifiers at the University of Washington School of Medicine: Building Institutional Consensus to Reduce Bias and Stigma.

Fam Med 2021 May;53(5):366-371

University of Washington Health Sciences Library, Seattle, WA.

Background And Objectives: Patient identifiers are used in the opening lines of case presentations and written documentation in health care and medical education settings. These identifiers can reflect physicians' implicit biases, which are known to impact patient care. Yet, no clear recommendations for the use of patient identifiers to reduce bias and stigma in patient care and medical education learning environments currently exist. We describe a process and outcomes for articulating such recommendations.

Methods: The University of Washington School of Medicine convened a group of diverse stakeholders to create patient identifier recommendations for use in the undergraduate medical education program. After a literature review, 22 recommendations for the use of patient identifiers were articulated. These underwent public comment periods reaching 11,150 potential respondents across our 5-state institution. Feedback from 437 respondents informed modifications to the recommendations. We used consensus methodology with three rounds of surveys and an expert group of 27 stakeholders to adopt recommendations with an a priori threshold of 90% agreeing the recommendation should be used.

Results: We adopted 12 recommendations for patient identifiers for age, gender/sex, race/ethnicity, sexual orientation, ability, size, and stigma; nine in round one, three in round two, and none in the third round.

Discussion: Our institution vetted these patient identifier recommendations via public comment and consensus methodology. Next steps include implementation across the undergraduate medical education program, including classroom and clinical settings. Other institutions could consider similar processes as key steps to reduce bias and stigma in their medical education programs.
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http://dx.doi.org/10.22454/FamMed.2021.251330DOI Listing
May 2021

Cytotoxic, genotoxic, and toxicogenomic effects of dihydroxyacetone in human primary keratinocytes.

Cutan Ocul Toxicol 2021 Sep 11;40(3):232-240. Epub 2021 Jun 11.

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD, USA.

Purpose: Dihydroxyacetone (DHA) is the only ingredient approved by the U.S. FDA as a colour additive in sunless tanning (self-tanning) products. Consumer sunless tanning products available for retail purchase contain 1-15% DHA. Although originally thought to only interact with the stratum corneum, more recent research has shown that DHA penetrates beyond the stratum corneum to living keratinocytes indicating a possible route of exposure in the epidermis.

Materials And Methods: Normal Human Epidermal Keratinocytes (NHEK) were used to determine any potential toxicological effects of DHA in the epidermis. NHEK cells exposed to DHA concentrations up to 0.90% (100 mM) in dosing media were evaluated for viability, genotoxicity (Comet Assay), and gene expression changes by microarray analysis.

Results: Cell viability significantly decreased ∼50% after 3-h exposure to 50 and 100 mM DHA. DNA damage was only found to be significantly increased in cells exposed to cytotoxic DHA concentrations. A subtoxic dose of DHA induced significant gene expression changes. Particularly, expression of cyclin B1, CDK1, and six other genes associated with the G2/M cell cycle checkpoint was significantly decreased which correlates well with a G2/M block reported in the existing literature. Advanced Glycation End Product (AGE) formation significantly increased after 24 h of DHA exposure at and above 10 mM. In summary, these data show that DHA is cytotoxic above 25 mM in primary keratinocytes. Genotoxicity was detected only at cytotoxic concentrations, likely indicative of non-biologically relevant DNA damage, while subtoxic doses induce gene expression changes and glycation.

Conclusion: DHA treatment had a significant and negative effect on primary keratinocytes consistent with cultured cell outcomes; however, more information is needed to draw conclusions about the biological effect of DHA in human skin.
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http://dx.doi.org/10.1080/15569527.2021.1931877DOI Listing
September 2021

Creation of the first national linked colorectal cancer dataset in Scotland: prospects for future research and a reflection on lessons learned.

Int J Popul Data Sci 2021 Mar 31;6(1):1654. Epub 2021 Mar 31.

Edinburgh Cancer Research Centre and Edinburgh Health Economics, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR.

Introduction: Current understanding of cancer patients, their treatment pathways and outcomes relies mainly on information from clinical trials and prospective research studies representing a selected sub-set of the patient population. Whole-population analysis is necessary if we are to assess the true impact of new interventions or policy in a real-world setting. Accurate measurement of geographic variation in healthcare use and outcomes also relies on population-level data. Routine access to such data offers efficiency in research resource allocation and a basis for policy that addresses inequalities in care provision.

Objective: Acknowledging these benefits, the objective of this project was to create a population level dataset in Scotland of patients with a diagnosis of colorectal cancer (CRC).

Methods: This paper describes the process of creating a novel, national dataset in Scotland.

Results: In total, thirty two separate healthcare administrative datasets have been linked to provide a comprehensive resource to investigate the management pathways and outcomes for patients with CRC in Scotland, as well as the costs of providing CRC treatment. This is the first time that chemotherapy prescribing and national audit datasets have been linked with the Scottish Cancer Registry on a national scale.

Conclusions: We describe how the acquired dataset can be used as a research resource and reflect on the data access challenges relating to its creation. Lessons learned from this process and the policy implications for future studies using administrative cancer data are highlighted.
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http://dx.doi.org/10.23889/ijpds.v6i1.1654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111382PMC
March 2021

Three Versus Six Months of Adjuvant Doublet Chemotherapy for Patients With Colorectal Cancer: A Multi-Country Cost-Effectiveness and Budget Impact Analysis.

Clin Colorectal Cancer 2021 09 15;20(3):236-244. Epub 2021 Apr 15.

Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland.

Background: The Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority, less toxicity, and cost-effectiveness from a UK perspective of 3 versus 6 months of oxaliplatin-based chemotherapy for patients with colorectal cancer. This study assessed the cost-effectiveness of shorter treatment and the budget impact of implementing trial findings from the perspectives of all countries recruited to SCOT: Australia, Denmark, New Zealand, Spain, Sweden, and the United Kingdom.

Patients And Methods: Individual cost-utility analyses were performed from the perspective of each country. Resource, quality of life, and survival estimates from the SCOT trial (N = 6065) were used. Probabilistic sensitivity analysis and subgroup analyses were undertaken. Using undiscounted costs from these cost-utility analyses, the impact on country-specific healthcare budgets of implementing the SCOT trial findings was calculated over a 5-year period. The currency used was US dollars (US$), and 2019 was the base year. One-way and scenario sensitivity analysis addressed uncertainty within the budget impact analysis.

Results: Three months of treatment were cost saving and cost-effective compared to 6 months from the perspective of all countries. The incremental net monetary benefit per patient ranged from US$8972 (Spain) to US$13,884 (Denmark). The healthcare budget impact over 5 years for the base-case scenario ranged from US$3.6 million (New Zealand) to US$61.4 million (UK) and totaled over US$150 million across all countries.

Conclusion: This study has widened the transferability of results from the SCOT trial, showing that shorter treatment is cost-effective from a multi-country perspective. The vast savings from implementation could fully justify the investment in conducting the SCOT trial.
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http://dx.doi.org/10.1016/j.clcc.2021.04.001DOI Listing
September 2021
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