bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paediatric ED utilisation in the early phase of the COVID-19 pandemic
Authors: Lee Lois , Mannix Rebekah , Guedj Romain , Chong Shu-Ling , Sunwoo Sidney , Woodward Tony , Fleegler Eric 
Published: December 2020

BackgroundPast epidemics, including influenza, have resulted in increased paediatric patient volume in EDs. During the early weeks of the COVID-19 pandemic, it was unclear how ED volume would be impacted in paediatric hospitals. The objective of this study was to examine differences in the international experience of paediatric ED utilisation and disposition at five different children’s hospitals.MethodsWe obtained data on ED volume, acuity level and disposition (hospitalisation and intensive care unit (ICU) admission) for the time period 1 December1–10 August for the years 2017–2020 from hospitals in five cities (Boston, Massachusetts, USA; Singapore; Melbourne, Australia; Seattle, Washington, USA; and Paris, France). Per cent change was analysed using paired t-tests or Wilcoxon signed rank test.ResultsOverall ED volume dramatically decreased in all five hospitals during the early months of COVID-19 compared with prior years. There was a more varied response of decreases in ED volume by acuity level, hospitalisation and ICU admission among the five hospitals. The one exception was a 2% increase in ICU admissions in Paris. As of August 2020, all hospitals have demonstrated increases in ED volume; however, they are still below baseline.ConclusionPaediatric EDs in these five cities demonstrated differential decreases of ED volume by acuity and disposition during the early months of the COVID-19 pandemic.
Post-exertion oxygen saturation as a prognostic factor for adverse outcome in patients attending the emergency department with suspected COVID-19: a substudy of the PRIEST observational cohort study
Authors: Goodacre Steve , Thomas Ben , Lee Ellen , Sutton Laura , Loban Amanda , Waterhouse Simon , Simmonds Richard , Biggs Katie , Marincowitz Carl , Schutter José , Connelly Sarah , Sheldon Elena , Hall Jamie , Young Emma , Bentley Andrew , Challen Kirsty , Fitzsimmons Chris , Harris Tim , Lecky Fiona , Lee Andrew , Maconochie Ian , Walter Darren 
Published: December 2020

BackgroundMeasurement of post-exertion oxygen saturation has been proposed to assess illness severity in suspected COVID-19 infection. We aimed to determine the accuracy of post-exertional oxygen saturation for predicting adverse outcome in suspected COVID-19.MethodsWe undertook a substudy of an observational cohort study across 70 emergency departments during the first wave of the COVID-19 pandemic in the UK. We collected data prospectively, using a standardised assessment form, and retrospectively, using hospital records, from patients with suspected COVID-19, and reviewed hospital records at 30 days for adverse outcome (death or receiving organ support). Patients with post-exertion oxygen saturation recorded were selected for this analysis. We constructed receiver-operating characteristic curves, calculated diagnostic parameters, and developed a multivariable model for predicting adverse outcome.ResultsWe analysed data from 817 patients with post-exertion oxygen saturation recorded after excluding 54 in whom measurement appeared unfeasible. The c-statistic for post-exertion change in oxygen saturation was 0.589 (95% CI 0.465 to 0.713), and the positive and negative likelihood ratios of a 3% or more desaturation were, respectively, 1.78 (1.25 to 2.53) and 0.67 (0.46 to 0.98). Multivariable analysis showed that post-exertion oxygen saturation was not a significant predictor of adverse outcome when baseline clinical assessment was taken into account (p=0.368). Secondary analysis excluding patients in whom post-exertion measurement appeared inappropriate resulted in a c-statistic of 0.699 (0.581 to 0.817), likelihood ratios of 1.98 (1.26 to 3.10) and 0.61 (0.35 to 1.07), and some evidence of additional prognostic value on multivariable analysis (p=0.019).ConclusionsPost-exertion oxygen saturation provides modest prognostic information in the assessment of selected patients attending the emergency department with suspected COVID-19.Trial registration numberISRCTN Registry (ISRCTN56149622)http://www.isrctn.com/ISRCTN28342533.
Development and initial psychometric validation of a patient-reported outcome measure for Crohn’s perianal fistula: the Crohn’s Anal Fistula Quality of Life (CAF-QoL) scale
Authors: Adegbola Samuel O , Dibley Lesley , Sahnan Kapil , Wade Tiffany , Verjee Azmina , Sawyer Rachel , Mannick Sameer , McCluskey Damian , Bassett Paul , Yassin Nuha , Warusavitarne Janindra , Faiz Omar , Phillips Robin , Tozer Phil J , Norton Christine , Hart Ailsa L 
Published: December 2020

IntroductionCrohn’s perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype.MethodsA draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn’s perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test–retest analysis.ResultsData from 211 patients contributed to development of a final 28-item questionnaire. The Crohn’s Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach’s alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS.ConclusionThe CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.
Risk factors for resignation from work after starting infertility treatment among Japanese women: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study
Authors: Imai Yuya , Endo Motoki , Kuroda Keiji , Tomooka Kiyohide , Ikemoto Yuko , Sato Setsuko , Mitsui Kiyomi , Ueda Yuito , Deshpande Gautam A , Tanaka Atsushi , Sugiyama Rikikazu , Nakagawa Koji , Sato Yuichi , Kuribayashi Yasushi , Itakura Atsuo , Takeda Satoru , Tanigawa Takeshi 
Published: December 2020

ObjectiveTo elucidate the risk factors associated with resignation from work of Japanese women undergoing infertility treatment.MethodsA total of 1727 female patients who attended a private fertility clinic in Japan participated in the Japan-Female Employment and Mental health in Assisted reproductive technology study. Questions related to demographic, clinical and socioeconomic characteristics were employed in the questionnaire. Out of the 1727 patients, 1075 patients who were working at the time of initiating infertility treatment and felt infertility treatment incompatible with work were included in the analysis. Risk factors for resignation were assessed by using multivariable logistic regression models.ResultsAmong 1075 working women who started infertility treatment, 179 (16.7%) subsequently resigned. Multivariable-adjusted ORs for resignation in those with lower educational background and infertility for ≥2 years were 1.58 (95% CI: 1.07 to 2.34) and 1.82 (95% CI: 1.15 to 2.89), respectively. The OR for resignation in non-permanent workers undergoing infertility treatment was 2.65 (95% CI: 1.61 to 4.37). While experiencing harassment in the workplace approached significance, lack of support from the company was significantly associated with resignation after starting infertility treatment, with ORs of 1.71 (95% CI: 0.98 to 2.99) and 1.91 (95% CI: 1.28 to 2.86), respectively.ConclusionOne-sixth of women resigned after starting infertility treatments. It was found that factors related to education, infertility duration and work environment were significantly associated with resignation. Reducing the physical and psychological burden endured by women, for example, by increasing employer-provided support, is vitally important in balancing infertility treatment with maintenance of work life.
Impact of enhanced personal protective equipment on the physical and mental well-being of healthcare workers during COVID-19
Authors: Swaminathan Ramanathan , Mukundadura Bimantha Perera , Prasad Shashi 
Published: December 2020

AbstractBackgroundThe COVID-19 pandemic has necessitated the use of enhanced personal protective equipment (PPE) in healthcare workers in patient-facing roles. We describe the impact on the physical and mental well-being of healthcare professionals who use enhanced PPE consistently.MethodsWe conducted a single-centre, cross-sectional study among healthcare professionals who use enhanced PPE. A web-based questionnaire was disseminated to evaluate the effects on individuals' physical and mental well-being. Physical and mental impact was assessed through a visual analogue scale.ResultsProspective analysis of the views of 72 respondents is reported. 63.9% were women and 36.1% were men. Physical impact included exhaustion, headache, skin changes, breathlessness and a negative impact on vision. Communication difficulties, somnolence, negative impact on overall performance and difficulties in using surgical instrumentation were reported.ConclusionOur study demonstrates the undeniable negative impact on the front-line healthcare workers using enhanced PPE and lays the ground for larger multicentric assessments given for it to potentially be the norm for the foreseeable future.
Quantifying the economic impact of disasters on businesses using human mobility data: a Bayesian causal inference approach
Authors: Yabe Takahiro , Zhang Yunchang , Ukkusuri Satish V. 
Published: December 2020

AbstractIn recent years, extreme shocks, such as natural disasters, are increasing in both frequency and intensity, causing significant economic loss to many cities around the world. Quantifying the economic cost of local businesses after extreme shocks is important for post-disaster assessment and pre-disaster planning. Conventionally, surveys have been the primary source of data used to quantify damages inflicted on businesses by disasters. However, surveys often suffer from high cost and long time for implementation, spatio-temporal sparsity in observations, and limitations in scalability. Recently, large scale human mobility data (e.g. mobile phone GPS) have been used to observe and analyze human mobility patterns in an unprecedented spatio-temporal granularity and scale. In this work, we use location data collected from mobile phones to estimate and analyze the causal impact of hurricanes on business performance. To quantify the causal impact of the disaster, we use a Bayesian structural time series model to predict the counterfactual performances of affected businesses (what if the disaster did not occur?), which may use performances of other businesses outside the disaster areas as covariates. The method is tested to quantify the resilience of 635 businesses across 9 categories in Puerto Rico after Hurricane Maria. Furthermore, hierarchical Bayesian models are used to reveal the effect of business characteristics such as location and category on the long-term resilience of businesses. The study presents a novel and more efficient method to quantify business resilience, which could assist policy makers in disaster preparation and relief processes.
Knowledge and Use of Caries Detection Methods among Dental Students and Dental Practitioners in Riyadh, Saudi Arabia
Authors: Radwan Waseem , AlNasser Abeer A. , Aloqab Hesah , Al-Saggaf Khalid , Almuhtab Nora A. , Alnasyan Bothinah 
Published: December 2020

Aim. Accurate detection and diagnosis of dental caries is an integral part of achieving adequate comprehensive dental care. Furthermore, the high prevalence of caries and generally poor oral health in Saudi Arabia is a public health concern. In addition to necessary preventive programs and awareness initiatives, understanding diagnostic practices plays an important role in garnering broad background knowledge regarding the routine diagnostic means utilized by our targeted respondents. Therefore, this study aimed to assess the methods of caries detection among dental students and dental practitioners in Riyadh using a cross-sectional observational study design. Methods. The sample comprised 496 dental students, interns, postgraduate residents, general dental practitioners, specialists, and consultants from the Riyadh region of Saudi Arabia. A survey was designed to assess caries detection methods, risk assessment practices, and knowledge of advanced diagnostic methods. The responses were correlated with demographic and educational variables. Regression models were used to predict associations. Results. 42.3% and 32.7% use sharp explorers in diagnosing caries always and most of the time, respectively. When conducting caries risk assessment practices, 64.4% was very likely to review the patient’s medical history and lifestyle. In terms of knowledge of advanced diagnostic methods, 47.8% know “much” to “very much” about FOTI. The knowledge of advanced caries diagnostic methods and practices of advanced diagnostic methods were significantly positively correlated (r = 0.388,

P
<
0.001

). Linear regression analysis indicated that higher experience (10+ years) was associated with higher knowledge regarding advanced caries diagnostic methods (

β

= 0.27,

P
=
0.009

). The mean rank for risk assessment practices was significantly lower in GPs compared to consultants

P
<
0.05

. Conclusions. The use of traditional and invasive methods of caries detection is prevalent among our respondents, while the usage of advanced diagnostic methods is for the most part low. Therefore, we advocate for more minimally invasive approaches and as such encourage the practice and availability of advanced diagnostic methods.
Abstract IA14: Increasing viral mimicry with vitamin C
Authors: Jones Peter A. 
Published: December 2020

Abstract
Responses of MDS patients to DNA methylation inhibitors (DNMTis) is due in part to the induction of expression of transposable elements, particularly endogenous retroviruses (ERVs). Induction of these transcripts leads to an innate immune response which may be responsible for the clinical efficacy of the drugs and we have called this “viral mimicry”. We investigated whether physiological concentrations of vitamin C given simultaneously with treatment with DNMTis would increase the expression of ERVs. The rationale being that the TET enzymes require vitamin C for their maximum activities, and we hypothesized that the induction of 5-hydroxymethylcytosine would stimulate the expression of these retroviruses. Experiments in culture showed that addition of vitamin C, strongly increases the expression of ERVs and increases the formation of 5-hydroxymethylcytosine during treatment. This is important since culture medium is mostly not supplemented with vitamin C. In more recent patient trials we have shown that responses to DNMTis may indeed be partially due to the induction of ERVs. Because we and others have shown that many patients in hematology clinics are severely vitamin C deficient, we are now exploring whether restoration of vitamin C levels to normal may potentiate the activities of the DNMTis. Preliminary data shows that oral administration of vitamin C increases the expression of ERVs and also the quantity of 5-hydroxymethylcytosine in the DNA of circulating cells. We have now designed a prospective clinical trial to test these hypothesis and preliminary data will be presented.
Citation Format: Peter A. Jones. Increasing viral mimicry with vitamin C [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA14.
Abstract PO-003: Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2
Authors: Greenberg Inbal , Klein Anat , Grossman Rachel , Sokol Ethan , Yeini Eilam , Ofek Paula , Satchi-Fainaro Ronit , Reuveni Hadas , Rubinek Tami , Wolf Ido 
Published: December 2020

Abstract
Brain metastases (BMs) from colorectal cancer (CRC) are currently the fourths leading cause of BMs, and their incidence is on the rise. Yet, mechanisms mediating the formation of BMs from CRC are unknown. We aimed to explore genomic drivers enabling tropism and adaptation of CRC cells to the brain environment and decipher mechanisms facilitating the process. We analyzed FoundationOne database, which contains genomic alterations data of cancer-related genes in over 16,000 human CRC primary and metastasis samples. Increased prevalence was noted in the insulin receptor substrate 2 (IRS2) gene, which was significantly amplified in BMs relative to primary tumors and other metastatic sites. IRS2 is a cytoplasmic adaptor mediating effects of insulin and IGF-1 receptors and is known to be involved in more aggressive behavior of different cancer types. In agreement with the genomic data, immunohistochemistry of human clinical samples showed increased expression of IRS2 protein in BMs. Next, we created an in-vitro system mimicking the brain microenvironment using human astrocytes or their conditioned media (CM). Under these conditions, IRS2-overexpressed CRC cells survived better and formed larger 3D spheres. IRS2-silenced CRC cells showed a mirror image. Furthermore, IRS2-overexpressed CRC cells generated larger brain lesions in an intracranial CRC BMs mice model. Interestingly, a transcriptomic analysis revealed significant enrichment of the AKT and β-catenin pathways by IRS2. Indeed, IRS2-amplified cells showed enhanced AKT phosphorylation and inhibition of PI3K or AKT using Alpelisib or Akt1/2 kinase inhibitor, respectively, effectively decreased their proliferation in CM. Importantly, IRS2-amplified cells had increased expression and transcriptional activity of the β-catenin, and AKT pathway inhibitors or IRS2 inhibitor (NT-219) had a more pronounced effect on the activity of β-catenin on those cells. These data indicate, for the first time, the unique genomic profile of CRC BMs and imply the IRS2 role in promoting CRC BMs. These effects may be mediated, at least in part, by modulation of the AKT and β-catenin pathway. These findings may pave the way for the development of novel therapeutic strategies to prevent BMs formation.
Citation Format: Inbal Greenberg, Anat Klein, Rachel Grossman, Ethan Sokol, Eilam Yeini, Paula Ofek, Ronit Satchi-Fainaro, Hadas Reuveni, Tami Rubinek, Ido Wolf. Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2 [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-003.
Abstract PO-019: DNA methylation status in a promoter region of the K-RAS gene in patients with Colorectal Cancer
Authors: Herrera-Pulido Jehison Alirio , Ricaurte-Guerrero Orlando , Acosta-Forero Jinneth , Moreno-Acosta Pablo , Sanabria-Salas María Carolina , Arboleda-Granados Humberto , Hernández Gustavo , Serrano-López Martha Lucía 
Published: December 2020

Abstract
Background: DNA methylation plays an important role in colorectal cancer (CRC) carcinogenesis. The mutated K-RAS gene has been reported to be crucial in CRC progression, but it is not known whether the wild-type gene is regulated by methylation and whether or not this mechanism contributes to disease progression. Now, there are not known reports about the methylation status of the distal K-RAS gene promoter in patients diagnosed with CRC. Materials and methods: Fifty-seven formalin-fixed, paraffin-embedded (FFPE) tissue samples from 57 patients diagnosed with CRC, without K-RAS mutation, were analyzed to determine the methylation status of the distal promoter of this gene. The analysis was performed by DNA extraction from laser microdissections, and 2 mm diameter punch, conversion with sodium bisulfite, amplification by nested PCR, and direct sequencing of purified PCR products. Results: Of the 57 cases, in 2 (6.25%) partial methylation was found in island 2 for one of the cases and in islands 1 and 2 for the other. In 30 (93.75%) cases no methylation was found and in the remaining 25 (43.85%) cases methylation could not be determined, probably due to the quantity and quality of DNA extracted from these blocks. Conclusion: The results found from the preliminary analysis of the methylation status of a region of the distal promoter of the K-RAS gene that serves as an anchorage to Sp1, allowed to determine a partial methylation status in 6.25% of the cases studied, concluding that methylation in this region is not a frequent event
Citation Format: Jehison Alirio Herrera-Pulido, Orlando Ricaurte-Guerrero, Jinneth Acosta-Forero, Pablo Moreno-Acosta, María Carolina Sanabria-Salas, Humberto Arboleda-Granados, Gustavo Hernández, Martha Lucía Serrano-López. DNA methylation status in a promoter region of the K-RAS gene in patients with Colorectal Cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-019.
Abstract PO-044: Epigenetic silencing of SLC17A7 promotes osteosarcoma growth
Authors: Nerlakanti Niveditha , McGuire Jeremy , Yu Diana , Reed Damon R. , Lynch Conor C. 
Published: December 2020

Abstract
Osteosarcoma is an orphan disease with only 900 patients diagnosed each year in US. Most patients are adolescents with small number of older patients. The 5-survival rates for those with metastatic disease is only 30%. Frustratingly, there has been little change in treatment options (chemotherapy, surgery and radiotherapy) due to the difficulty of conducting clinical trials in this rare but deadly cancer. To address this, strong pre-clinical trial information is required to motivate clinical trial design. In vitro and in vivo, we identified that the pan-HDAC inhibitor, panobinostat is highly effective in limiting osteosarcoma growth and metastasis. Panobinostat is approved for the treatment of other malignancies but has noted toxicities. Therefore, to identify therapeutic targets, we explored the HDACs responsible for driving osteosarcoma metastasis and the specific genes through which those HDACs mediated their effects. Our data shows that HDAC1 and HDAC2 are key for osteosarcoma survival using siRNA approaches. Use of the HDAC1/2 selective inhibitor romidepsin in vitro and in vivo supported this finding. To identify targets being regulated by HDAC1/2, we performed microarray and proteomics analyses on romidepsin treated osteosarcoma cells. We found and validated independently that, SLC17A7, a metabolic vesicular glutamate transporter to be highly induced in response to romidepsin treatment; &gt;100 fold more than base line in multiple osteosarcoma cell lines. Functionally, SLC17A7 allows entry of glutamate into the synaptic vesicles from cytoplasm and releases the glutamate from the cells via exocytosis. In our studies, we have seen that romidepsin treatment leads to reduced glutamate levels in the conditioned media and cell death indicating key roles for SLC17A7 in driving osteosarcoma progression and metastasis. In conclusion, our data shows that HDAC1/2 suppression of SLC17A7 is a novel means of promoting osteosarcoma progression and metastasis.
Citation Format: Niveditha Nerlakanti, Jeremy McGuire, Diana Yu, Damon R. Reed, Conor C. Lynch. Epigenetic silencing of SLC17A7 promotes osteosarcoma growth [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-044.