bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical care ultrasound training: a survey exploring the “education gap” between potential and reality in Canada
Authors: Slemko Jocelyn M. , Daniels Vijay J. , Bagshaw Sean M. , Ma Irene W. Y. , Brindley Peter G. , Buchanan Brian M. 
Published: December 2021

Abstract
Background
Critical care ultrasound (CCUS) is now a core competency for Canadian critical care medicine (CCM) physicians, but little is known about what education is delivered, how competence is assessed, and what challenges exist. We evaluated the Canadian CCUS education landscape and compared it against published recommendations.

Methods
A 23-item survey was developed and incorporated a literature review, national recommendations, and expert input. It was sent in the spring of 2019 to all 13 Canadian Adult CCM training programs via their respective program directors. Three months were allowed for data collection and descriptive statistics were compiled.

Results
Eleven of 13 (85%) programs responded, of which only 7/11 (64%) followed national recommendations. Curricula differed, as did how education was delivered: 8/11 (72%) used hands-on training; 7/11 (64%) used educational rounds; 5/11 (45%) used image interpretation sessions, and 5/11 (45%) used scan-based feedback. All 11 employed academic half-days, but only 7/11 (64%) used experience gained during clinical service. Only 2/11 (18%) delivered multiday courses, and 2/11 (18%) had mandatory ultrasound rotations. Most programs had only 1 or 2 local CCUS expert-champions, and only 4/11 (36%) assessed learner competency. Common barriers included educators receiving insufficient time and/or support.

Conclusions
Our national survey is the first in Canada to explore CCUS education in critical care. It suggests that while CCUS education is rapidly developing, gaps persist. These include variation in curriculum and delivery, insufficient access to experts, and support for educators.
Accelerated nonstandard finite difference method for singularly perturbed Burger-Huxley equations
Authors: Kabeto Masho Jima , Duressa Gemechis File 
Published: December 2021

AbstractObjectiveThe main purpose of this paper is to present an accelerated nonstandard finite difference method for solving the singularly perturbed Burger-Huxley equation in order to produce more accurate solutions.ResultsThe quasilinearization technique is used to linearize the nonlinear term. A nonstandard methodology of Mickens procedure is used in the spatial direction and also within the first order temporal direction that construct the first-order finite difference approximation to solve the considered problem numerically. To accelerate the rate of convergence from first to second-order, the Richardson extrapolation technique is applied. Numerical experiments were conducted to support the theoretical results.
Interferon-γ induces interleukin-6 production by neutrophils via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway
Authors: Yoshida Shuhei , Yamada Shunya , Yokose Kohei , Matsumoto Haruki , Fujita Yuya , Asano Tomoyuki , Matsuoka Naoki , Temmoku Jumpei , Sato Shuzo , Yoshiro-Furuya Makiko , Watanabe Hiroshi , Migita Kiyoshi 
Published: December 2021

Abstract
Objective
Interferon-gamma (IFN-γ) is overexpressed in rheumatoid synovium and thought to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we examined our hypothesis that IFN-γ activates innate immune cells and upregulates inflammatory cytokines. Peripheral blood neutrophils were stimulated with IFN-γ in the presence or absence of Janus kinase (JAK) inhibitors. Interleukin-6 (IL-6) mRNA and protein expression were analyzed using real-time polymerase chain reaction (PCR) method and enzyme-linked immunosorbent assay. Protein phosphorylation of JAKs or STAT1 was assessed by Western blot using phospho-specific antibodies.

Results
IFN-γ stimulation induces IL-6 expression in protein and mRNA levels in human neutrophils. Furthermore, IFN-γ stimulation induces JAK1/JAK2 phosphorylation and downstream signal transducer and activator of transcription (STAT) 1 phosphorylation in human neutrophils. Although all JAKi, blocked IFN-γ-induced JAK1.2/STAT1 phosphorylation at higher concentrations (100 nM), baricitinib most efficiently inhibited IFN-γ-induced JAK1.2/STAT1 phosphorylation at lower concentrations (≤ 25 nM). Among these JAKi, baricitinib was the most potent regulator for IFN-γ-induced IL-6 production in human neutrophils. Our data indicate that IFN-γ upregulates IL-6 production via the JAK1/2-STAT1 pathway in human innate immune cells. Furthermore, this IFN-γ-mediated IL-6 induction via JAK/STAT was downregulated by JAKi.
Genome-wide methylation patterns in Marfan syndrome
Authors: van Andel Mitzi M. , Groenink Maarten , van den Berg Maarten P. , Timmermans Janneke , Scholte Arthur J. H. A. , Mulder Barbara J. M. , Zwinderman Aeilko H. , de Waard Vivian 
Published: December 2021

Abstract
Background
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process.

Methods
The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed.

Results
We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p < 10–8 or p < 10–6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before.

Conclusion
This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.
Infiltrative pattern of metastatic invasive lobular breast carcinoma in the abdomen: a pictorial review
Authors: Wong Ying Mei , Jagmohan Pooja , Goh Yong Geng , Putti Thomas Choudary , Ow Samuel Guan Wei , Thian Yee Liang , Pillay Premilla 
Published: December 2021

AbstractInvasive lobular carcinoma (ILC) has a greater tendency to metastasize to the peritoneum, retroperitoneum, and gastrointestinal (GI) tract as compared to invasive carcinoma of no special type (NST). Like primary ILC in the breast, ILC metastases are frequently infiltrative and hypometabolic, rather than mass forming and hypermetabolic in nature. This renders them difficult to detect on conventional and metabolic imaging studies. As a result, intra-abdominal ILC metastases are often detected late,
with patients presenting with clinical complications such as liver failure, hydronephrosis, or bowel obstruction. In patients with known history of ILC, certain imaging features are very suggestive of infiltrative metastatic ILC. These include retroperitoneal or peritoneal nodularity and linitis plastica appearance of the bowel. Recognition of linitis plastica on imaging should prompt deep or repeat biopsies. In this pictorial review, the authors aim to familiarize readers with imaging features and pitfalls for evaluation of intra-abdominal metastatic ILC. Awareness of these will allow the radiologist to assess these patients with a high index of suspicion and aid detection of metastatic disease. Also, this can direct histopathology and immunohistochemical staining to obtain the correct diagnosis in suspected metastatic disease.
Using amide proton transfer-weighted MRI to non-invasively differentiate mismatch repair deficient and proficient tumors in endometrioid endometrial adenocarcinoma
Authors: Li Yuan , Liu Xinyu , Wang Xiaoqi , Lin Chengyu , Qi Yafei , Chen Bo , Zhou Hailong , Wu Qiaoling , Ren Jing , Zhao Jia , Yang Junjun , Xiang Yang , He Yonglan , Jin Zhengyu , Xue Huadan 
Published: December 2021

AbstractObjectivesTo investigate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging to differentiate mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors in endometrioid endometrial adenocarcinoma (EEA).MethodsForty-nine patients with EEA underwent T1-weighted imaging, T2-weighted imaging, 3D APTw imaging, and diffusion-weighted imaging at 3 T MRI. Image quality and measurement confidence of APTw images were evaluated on a 5-point Likert scale. APTw and apparent diffusion coefficient (ADC) values were calculated and compared between the dMMR and pMMR groups and among the three EEA histologic grades based on the Federation of Gynecology and Obstetrics (FIGO) grading system criteria. Student’s t-test, analysis of variance with Scheffe post hoc test, and receiver operating characteristic analysis were performed. Statistical significance was set atp < 0.05.ResultsThirty-five EEA patients (9 with dMMR tumors and 26 with pMMR tumors) with good image quality were enrolled in quantitative analysis. APTw values were significantly higher in the dMMR group than in the pMMR group (3.2 ± 0.3% and 2.8 ± 0.5%, respectively;p = 0.019). ADC values of the dMMR and pMMR groups were 0.874 ± 0.104 × 10−3mm2/s and 0.903 ± 0.100 × 10−3mm2/s, respectively. No significant between-group difference was noted (p = 0.476). No statistically significant differences were observed in APTw values or ADC values among the three histologic grades (p = 0.766 andp = 0.295, respectively).ConclusionsAPTw values may be used as potential imaging markers to differentiate dMMR from pMMR tumors in EEA.
Prediction of small-molecule compound solubility in organic solvents by machine learning algorithms
Authors: Ye Zhuyifan , Ouyang Defang 
Published: December 2021

AbstractRapid solvent selection is of great significance in chemistry. However, solubility prediction remains a crucial challenge. This study aimed to develop machine learning models that can accurately predict compound solubility in organic solvents. A dataset containing 5081 experimental temperature and solubility data of compounds in organic solvents was extracted and standardized. Molecular fingerprints were selected to characterize structural features. lightGBM was compared with deep learning and traditional machine learning (PLS, Ridge regression, kNN, DT, ET, RF, SVM) to develop models for predicting solubility in organic solvents at different temperatures. Compared to other models, lightGBM exhibited significantly better overall generalization (logS  ± 0.20). For unseen solutes, our model gave a prediction accuracy (logS  ± 0.59) close to the expected noise level of experimental solubility data. lightGBM revealed the physicochemical relationship between solubility and structural features. Our method enables rapid solvent screening in chemistry and may be applied to solubility prediction in other solvents.
Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study
Authors: Dhaliwal Amritpal , Williams Felicity R. , Quinlan Jonathan I. , Allen Sophie L. , Greig Carolyn , Filer Andrew , Raza Karim , Ghosh Subrata , Lavery Gareth G. , Newsome Philip N. , Choudhary Surabhi , Breen Leigh , Armstrong Matthew J. , Elsharkawy Ahmed M. , Lord Janet M. 
Published: December 2021

Abstract
Background
Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use.

Methods
This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis.

Discussion
This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups.

Ethics and dissemination
The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server.

Trial registration
ClinicalTrials.gov Identifier: NCT04734496
Association between mortality and age among mechanically ventilated COVID-19 patients: a Japanese nationwide COVID-19 database study
Authors: Tanaka Chie , Tagami Takashi , Nakayama Fumihiko , Kudo Saori , Takehara Akiko , Fukuda Reo , Kaneko Junya , Ishiki Yoshito , Sato Shin , Shibata Ami , Kuno Masamune , Unemoto Kyoko , Hojo Masayuki , Mizoue Tetsuya , Asai Yusuke , Suzuki Setsuko , Ohmagari Norio 
Published: December 2021

Abstract
Background
Only a few studies have reported the association between age and mortality in COVID-19 patients who require invasive mechanical ventilation (IMV). We aimed to evaluate the effect of age on COVID-19-related mortality among patients undergoing IMV therapy.

Methods
This cohort study was conducted using the COVID-19 Registry Japan database, a nationwide multi-centre study of hospitalized patients with laboratory-confirmed COVID-19. Of all 33,808 cases registered between 1 January 2020 to 28 February 2021, we analysed 1555 patients who had undergone IMV. We evaluated mortality rates between age groups using multivariable regression analysis after adjusting for known potential components, such as within-hospital clustering, comorbidities, steroid use, medication for COVID-19, and vital signs on admission, using generalized estimation equation.

Results
By age group, the mortality rates in the IMV group were 8.6%, 20.7%, 34.9%, 49.7% and 83.3% for patients in their 50s, 60s, 70s, 80s, and 90s, respectively. Multivariable analysis showed that compared with those for patients aged < 60 years, the odds ratios (95% confidence interval) of death were 2.6 (1.6–4.1), 6.9 (4.2–11.3), 13.2 (7.2–24.1), 92.6 (16.7–515.0) for patients in their 60s, 70s, 80s, and 90s, respectively.

Conclusions
In this cohort study, age had a great effect on mortality in COVID-19 patients undergoing IMV, after adjusting for variables independently associated with mortality. This study suggested that age was associated with higher mortality and that preventing progression to severe COVID-19 in elderly patients may be a great public health issue.
Rural opioid treatment program patient perspectives on take-home methadone policy changes during COVID-19: a qualitative thematic analysis
Authors: Levander Ximena A. , Hoffman Kim A. , McIlveen John W. , McCarty Dennis , Terashima Javier Ponce , Korthuis P. Todd 
Published: December 2021

Abstract
Background
In the United States, methadone for opioid use disorder (OUD) is highly regulated. Federal agencies announced guidelines in March 2020 allowing for relaxation of take-home methadone dispensing at opioid treatment programs (OTPs) to improve treatment access and reduce COVID-19 transmission risk during the public health emergency. We explored patient perspectives at three OTPs serving rural communities on how take-home policy changes were received and implemented and how these changes impacted their addiction treatment and recovery.

Methods
We completed semi-structured individual qualitative interviews in 2 phases: (1) August–October 2020 and (2) November 2020–January 2021 (total n = 46), anticipating possible policy changes as the pandemic progressed. We interviewed patients with OUD enrolled at 3 rural OTPs in Oregon. Participants received varying take-home methadone allowances following the COVID-19-related policy changes. All interviews were conducted via phone, audio-recorded, and transcribed. We conducted a thematic analysis, iteratively coding transcripts, and deductively and inductively generating codes.

Results
The 46 participants included 50% women and 89% had Medicaid insurance. Three main themes emerged in the analysis, with no differences between study phases: (1) Adapting to changing OTP policies throughout the pandemic; (2) Recognizing the benefits, and occasional struggles, with increased take-home methadone dosing; and (3) Continuing policies and procedures post-pandemic. Participants described fears and anxieties around ongoing methadone access and safety concerns prior to OTP policy changes, but quickly adapted as protocols soon seemed “natural.” The majority of participants acknowledged significant benefits to increased take-homes independent of reducing COVID-19 infection risk including feeling “more like a normal person,” improved recovery support, reduced time traveling, and having more time with family and for work. Looking to a post-pandemic future, participants thought some COVID-19-related safety protocols should continue that would reduce risk of other infections, make OTP settings less stressful, and result in more individualized care.

Conclusions
As the pandemic progressed, study participants adapted to rapidly changing OTP policies. Participants noted many unanticipated benefits to increased take-home methadone and other COVID-19 protocols including strengthened self-efficacy and recovery and reduced interpersonal conflict, with limited evidence of diversion. Patient perspectives should inform future policies to better address the ongoing overdose epidemic.
Crisis hazard assessment for snow-related lahars from an unforeseen new vent eruption: the 2018 eruption of Kusatsu-Shirane volcano, Japan
Authors: Kataoka Kyoko S. , Tsunematsu Kae , Matsumoto Takane , Urabe Atsushi , Kawashima Katsuhisa 
Published: December 2021

AbstractTwo-thirds of the 111 active volcanoes in Japan are covered with snow for several months during winter and demonstrate high hazard and risk potentials associated with snow-related lahars during and after eruptions. On 23 January 2018, a sudden phreatic eruption occurred at the ski field on Kusatsu-Shirane (Mt. Motoshirane) volcano, Japan. This new vent eruption from the snow-clad pyroclastic cone required forecasting of future snow-related lahars and crisis hazards zonation of downslope areas including Kusatsu town, a popular tourist site for skiing and hot springs. In order to achieve a prompt hazard assessment for snow-related lahars, a multidisciplinary approach was carried out involving characterization of proximal tephra deposits, snow surveys, and numerical lahar flow simulations using the Titan2D model. To determine the input parameters for the flow model, the consideration of snow water equivalent (SWE) immediately after the eruption (on 29 January) and in the post-eruptive period (on 12 March), was significant. In the case of Kusatsu-Shirane volcano during the winter of 2018, linear relationships between altitude and SWE, obtained at different elevations, were used to estimate the snow volume around the new vents. Several scenarios incorporating snow and snowmelt (water), with or without the occurrence of a new eruption, were simulated for the prediction of future lahars. Three lahar scenarios were simulated, including A) rain-on-snow triggered, B) ice/snow slurry, and C) full snowmelt triggered by a new eruption, and indicated the flow paths (inundation areas) and travel distances. These were useful for lahar hazard zonation and identification of potential high-risk areas. Since the input parameters required for the Titan2D flow model can be relatively easily determined, the model was suitable for the 2018 eruption at Motoshirane where historical and geological lahar records are not available for calibration. The procedure used in the study will enable rapid lahar prediction and hazard zonation at snow-clad volcanoes. Further consideration for simulating a cohesive-type flow, which was predicted by the primary deposits containing large amounts of clay minerals and could not be expressed in the Titan2D flow model, is necessary.
The numerical simulation of the generation of lower-band VLF chorus using a quasi-broadband Vlasov Hybrid Simulation code
Authors: Nunn David 
Published: December 2021

AbstractIn this paper, we perform the numerical modelling of lower-band VLF chorus in the earth’s magnetosphere. Assuming parallel propagation the 1d3v code has one spatial dimension z along the ambient magnetic field, which has a parabolic z dependence about the equator. The method used is Vlasov Hybrid Simulation (VHS) also known in the literature as the method of Kinetic Phase Point Trajectories (Nunn in Computer Physics Comms 60:1–25, 1990, J Computational Phys 108(1):180–196, 1993; Kazeminezhad et al. in Phys Rev E67:026704, 2003). The method is straightforward and easy to program, and robust against distribution function filamentation. Importantly, VHS does not invoke unphysical smoothing of the distribution function. Previous versions of the VLF/VHS code had a narrow bandwidth ~ 100 Hz, which enabled simulation of a wide variety of discrete triggered emissions. The present quasi-broadband VHS code has a bandwidth of ~ 3000 Hz, which is far more realistic for the simulation of chorus in its entirety. Further, the quasi-broadband code does not require artificial saturation, and does not need to employ matched filtering to accommodate large spatial frequency gradients. The aim of this paper which has been achieved is to produce VLF chorus Vlasov simulations employing a systematic variety of triggering input signals, namely key down, single pulse, PLHR, and broadband hiss.
Graphical Abstract