bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB024: Cancer stem cells are enriched in human recurrent glioblastoma
Authors: Xie Xuanhua Peter , Ganbold Mungunsarnai , Pedraza Alicia , Parada Luis
Published: June 2022

A number of studies have described an essential role of cancer stem cells (CSC) in glioblastoma (GBM) progression and recurrence based on isolation by candidate markers. However, a systematic evaluation of the proposed CSC in paired human primary and recurrent glioblastoma has been lacking and whether they represent a unified cell type with conserved features over tumor evolution is unresolved. In this study, we used human patient derived xenografts (PDX) to investigate the status of these cells in patients following therapeutics and recurrence. Firstly, to ensure the fidelity of tumor heterogeneity in serially passaged orthotopic GBM PDX, we collected samples at different passages and performed whole tumor single cell RNA sequencing analysis. The results illustrate the preservation of all unsupervised transcriptional cell clusters through multiple passages. Furthermore, treatment of tumor bearing mice with temozolomide, the standard of care chemotherapeutic drug for glioblastoma patients, increased apoptosis and decreased tumor cell burden but spared CSC. We then turned to paired human primary and recurrent GBM samples to inquire cancer stem cell marker expression and cell distribution. In all three pairs of PDX studied, cancer stem cell marker F3 serves as a reliable means to isolate sphere formation cells and is augmented in the recurrent samples. Inspection of whole tumors with single cell RNA sequencing nails down the enrichment of CSC in recurrent tumors, thus emphasizing the importance to eradicate these cells in future therapeutics.

Citation Format: Xuanhua Peter Xie, Mungunsarnai Ganbold, Alicia Pedraza, Luis Parada. Cancer stem cells are enriched in human recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB024.
Abstract LB051: IL-6 and CCL18 mediate reciprocal interactions between VHL-deficient kidney cells and macrophages during development of ccRCC
Authors: Hsu Tien , Nguyen Thi Ngoc , Nguyen-Tran Hieu-Huy , Chen Chen-Yun
Published: June 2022

Loss of the von Hippel-Lindau (VHL) tumor suppressor gene function accounts for 70-80% of all clear-cell renal cell carcinoma (ccRCC) cases, the most prevalent form of RCC. Accumulating evidence has indicated that ccRCC arises at the site of chronic inflammation; however, how the ccRCC tumor cells interact with the immune components of the microenvironment has remained unclear. In this study we employed unbiased proteomic and genomic analyses on components of the tumor microenvironment under different conditions. We have identified the molecular and cellular mechanisms that underlie the crosstalk between VHL-deficient kidney tubule cells and macrophages with relevance to tumor-associated inflammation and ccRCC development. We demonstrate that the VHL-deficient non-cancerous kidney epithelial cells, representing the early stage of ccRCC initiation, secrete IL-6 that recruits macrophages and induces their polarization toward the pro-tumorigenic M2 phenotype in vitro and in the mouse Vhlh gene conditional knockout model. The activated human macrophages reciprocally secrete CCL18 and TGF-beta1 to stimulate epithelial-to-mesenchymal transition (EMT) of the kidney tubule cells. Importantly, treatment with anti-IL-6 neutralizing antibody can rescue inflammatory, proliferative, and EMT phenotypes of Vhlh conditional knockout in vivo. Furthermore, in a human ccRCC xenograft model, exogenous human macrophages can significantly promote primary tumor growth and metastasis; and this oncogenic function is dependent on the expression of CCL18. These findings identify specific factors involved in a reciprocal crosstalk between the tumor cells and the immune components such as macrophages in the microenvironment. These results thus suggest an avenue for early intervention of ccRCC.

Citation Format: Tien Hsu, Thi Ngoc Nguyen, Hieu-Huy Nguyen-Tran, Chen-Yun Chen. IL-6 and CCL18 mediate reciprocal interactions between VHL-deficient kidney cells and macrophages during development of ccRCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB051.
Abstract LB059: Subtype classification of pediatric high-grade glioma tumors by comparative transcriptomics
Authors: Mawla Gina D. , Lyle A. Geoffrey , Kephart Ellen T. , Learned Katrina , Beale Holly C. , Goldford Joshua E. , Vaske Olena M.
Published: June 2022

Pediatric high-grade glioma (pHGG) is a highly malignant and poorly understood cancer driven by diverse genetic and epigenetic mechanisms. Here, we use comparative RNA sequencing, outlier analysis, and spectral clustering approaches to analyze transcriptomic data of 1,543 pediatric brain tumor specimens from the UCSC Treehouse Childhood Cancer Initiative (Treehouse) and Open Pediatric Brain Tumor Atlas (OpenPBTA) to identify subpopulations of pHGG patients with characteristic gene expression profiles. We find that approximately half (45%) of pHGG tumors from OpenPBTA exist in three subgroups defined by high outlier-level expression either of: mitochondrially-encoded 12S and 16S rRNAs; genes enriched in the HSF1-mediated heat shock response and activation pathways; or six C/D box snoRNA (SNORD) genes originating from the paternally-expressed SNORD116 locus involved in Prader-Willi syndrome, a complex neurodevelopmental disorder. Interestingly, the same set of HSF1-dependent pathway genes is also significantly upregulated in a subset (~11%) of pHGG tumors from Treehouse, validating this finding in two independent compendia with different transcript isolation strategies (Treehouse, polyA selection; OpenPBTA, ribodepletion). Our work identifies distinct classes of tumors with outlier-level expression of genes with previously unknown roles in pHGG and provides a framework for subtyping tumors by comparative transcriptomics that is adaptable to any cancer type. We are currently investigating the molecular roles of HSF1-response genes and the imprinted SNORD116 gene cluster in pHGG. Our ongoing research into the biomolecular signatures and mechanisms of the three major tumor classes of pHGG as defined in our study will contribute to a greater understanding of pHGG disease manifestation and progression, and will inform strategies of tailored therapeutic interventions for children with this devastating disease.

Citation Format: Gina D. Mawla, A. Geoffrey Lyle, Ellen T. Kephart, Katrina Learned, Holly C. Beale, Joshua E. Goldford, Olena M. Vaske. Subtype classification of pediatric high-grade glioma tumors by comparative transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB059.
Abstract LB110: Twist pan-cancer synthetic reference materials for cell-free DNA (cfDNA) assay development
Authors: Cherry Patrick D.
Published: June 2022

Liquid biopsies hold great promise in reducing the burden of the disease of cancer on patients. Early detection of cancer via the cell free DNA represents the broadest vision and requires highly specificity. Ongoing disease monitoring is another important application of liquid biopsy and requires high sensitivity. Assay development requires analytical validation, and assays must be monitored for ongoing performance. These assays demand reference materials at specific variant allele frequencies for the assessment of specificity and sensitivity. Previously, obtaining reference materials was a laborious process of finding or engineering mutant cell lines. Here, we describe the design, manufacture, and quality control of a synthetic reference standard: the Twist Pan-Cancer Reference Standards, developed using Twist’s proprietary DNA printing platform to include a wide selection of both common and rare cancer targets for analytical validation. The reference material closely mimics the size distribution and content of cell-free DNA, with a primary peak at 167 bp and a secondary peak at 334 bp. The background cfDNA is derived from a single donor and highly characterized through NGS. The reference standard includes over 400 variant sites across 84 genes, including literature-curated, clinically-relevant variant sites. Additional panel-wide variants were included to aid in troubleshooting capture panels. The variant DNA is synthetically printed at 167 bp ± 5 bp and tiles over the site with extensive overlap, providing diversity of DNA termini relative to the position of the site of variation. Variant sites were printed and quantified independently so they can be pooled uniformly. NGS quality controls are implemented at multiple steps to ensure quality. The final products are available in a variant allele frequency (VAF) dilution series. The dilution series is quality controlled using droplet digital PCR (ddPCR) to ensure precision of variant allele frequencies. The Twist Pan Cancer Reference Standards provide a valuable solution for NGS-based assay developers seeking reference materials for a wide array of cancer variants, advancing adoption of liquid biopsy tests toward routine clinical practice.

Citation Format: Patrick D. Cherry. Twist pan-cancer synthetic reference materials for cell-free DNA (cfDNA) assay development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB110.
Abstract LB524: Discovery of highly selective RON kinase inhibitors
Authors: Ham Young Jin , Kim GyeongHwan , Lee Juhyun , Lee Jaeyoung , Kim Min Kyung , Kim Sunhong , Kim Woosook , Kim Han Byoul , Jang Sung Woong , Park Hee Dong , Jeon Seonguk , Kim Seok-Joo , Cho Joongheui , Kim Jungjoon , Yoon Hong bin , Kwak Youngshin
Published: June 2022

RON is a receptor tyrosine kinase of the MET proto-oncogene family, known as macrophage stimulating 1 receptor (MST1R) that recognizes macrophage-stimulating protein (MSP). RON has been known to be highly expressed in several epithelial tumors, promoting tumor progression and metastasis, and on macrophages surface, facilitating M2-like phenotype polarization of tumor-associated macrophages (TAM) to impair anti-tumor functions of CD8+ T cells. Although pharmacological inhibition of RON kinase has received attention from many research groups, monoclonal antibody drug showed a limited clinical efficacy due to RON variant of receptor region. Because the structure homology of kinase domain between RON and MET is 80%, discovery of RON-specific small molecule inhibitor is considered to be highly challenging to achieve. At first, we discovered a lead compound with about 50-fold of RON selectivity against MET kinase. Our medicinal chemistry efforts elevated RON/MET selectivity up to 500~10,000-fold (IC50 = 1~50 nM in RON enzyme assay), and the target specificity was proved through a panel assay of 372 kinases (Reaction Biology Corp.). A series of compounds effectively modulated p-RON and downstream signals (e.g. p-ERK and p-AKT) in MDA-MB-453, and inhibited cell proliferation of Ba/F3 cell-line engineered with human RON kinase. Significant anti-tumor effects were shown in syngeneic mouse models compared to a control group after oral administration, and studies related to immuno-oncology are ongoing in in-vitro or ex-/in-vivo assay systems. In conclusion, we have identified RON selective small molecule inhibitors that will be useful to figure out the biology following RON selective inhibition against MET kinase, and to validate the translational potential of RON kinase as a therapeutic target for human diseases including cancer.

Citation Format: Young Jin Ham, GyeongHwan Kim, Juhyun Lee, Jaeyoung Lee, Min Kyung Kim, Sunhong Kim, Woosook Kim, Han Byoul Kim, Sung Woong Jang, Hee Dong Park, Seonguk Jeon, Seok-Joo Kim, Joongheui Cho, Jungjoon Kim, Hong bin Yoon, Youngshin Kwak. Discovery of highly selective RON kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB524.
Abstract LB539: Development of GB2102, a novel and highly differentiated anti-FGFR2b antibody for the treatment of gastric cancer
Authors: Zhou Tiantian , Du Qinglin , Yang Xueyan , Peng Fei , Li James , Han Shuhua
Published: June 2022

Background: Gastric cancer (GC) is a complex and heterogeneous disease with limited available treatment options. Fibroblast growth factor receptor-2b (FGFR2b) is overexpressed in approximately 2-30% of GC and associated with worse prognosis. Bemarituzumab is an afucosylated humanized monoclonal antibody that specifically inhibits FGFR2b. In the FIGHT trial, bemarituzumab showed beneficial response in GC, but appeared to cause high corneal adverse events. It was hypothesized that FGF10 inhibition may be the mechanism of corneal toxicity by bemarituzumab. We have recently generated a monoclonal antibody against FGFR2b with potent FGF7 blocking activity but weak inhibition activity for FGF10. Thus, GB2102 may represent a differentiated antibody therapeutics that has a potential to decrease the adverse effects in the eyes. Methods: GB2102 was generated by immunization of FGFR2b protein in mice followed by hybridoma technique. FGF7 and FGF10 ligand blocking was assessed by ELISA. FGF7-induced FGFR2b phosphorylation and cell proliferation were studied in SNU-16 gastric cancer tumor cell line. Antibody-dependent cell-mediated cytotoxicity (ADCC) function was evaluated by IL-2-activated NK cell-induced lysis of target cells. Results: GB2102 displayed potent blocking of FGF7-FGFR2b pathway by inhibition of FGF7-induced FGFR2b phosphorylation and tumor cell proliferation. But GB2102 showed weak blocking of FGF10 binding to FGFR2b compared with benchmark, suggesting that GB2102 may have better safety profile in corneal toxicity. In ADCC function assay, GB2102 induced potent ADCC effects by primary human NK cells to kill FGFR2b-expressing tumor cells. Conclusions: In summary, preclinical studies showed that GB2102 is an anti-FGFR2b antibody with potent ADCC effect and strong FGF7 blocking but weak FGF10 inhibition. These results suggest that GB2102 is potentially a safe and effective candidate for the treatment of FGFR2b positive gastric cancer.

Citation Format: Tiantian Zhou, Qinglin Du, Xueyan Yang, Fei Peng, James Li, Shuhua Han. Development of GB2102, a novel and highly differentiated anti-FGFR2b antibody for the treatment of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB539.
Irisin Protects Cerebral Neurons from Hypoxia/Reoxygenation via Suppression of Apoptosis and Expression of Pro-Inflammatory Cytokines
Authors: Yu Qian , Li Guangyao , Li Jiangjing , Sun Li , Yang Yonghui , Tao Lei
Published: June 2022

Background: Ischemic stroke is a major health issue that causes high incidents of morbidity and mortality worldwide. Irisin is an excise-induced protein that has exhibited pleiotropic properties. Accumulating evidence reveals its critical roles in the regulation of various cellular functions, including nervous system functions. This study aims to disclose the effect of irisin on rat cerebral neurons suffering from hypoxia/reoxygenation (H/R) treatment and to explore the potential underlying molecular mechanisms. Methods: The percentage of rat cerebral neuron cell death was determined by flow cytometry analysis and MTT assay. The expression levels of target genes were measured by western blotting and real-time quantitative reverse transcription PCR assay. Results: Our results demonstrated that irisin treatment substantially reduced H/R-induced apoptosis of rat cerebral neurons. Further investigation revealed that irisin treatment markedly decreased mitogen-activated protein kinase (MAPK) signaling pathway activation and suppressed pro-informatory cytokine expression in cerebral neurons with H/R challenge. Finally, we showed that the neuroprotective effect and anti-inflammatory effect of irisin were comparable with three MAPK signaling inhibitors. Conclusion: Irisin exerts profound neuroprotective and anti-inflammatory effects on H/R-stimulated cerebral neurons by inhibiting the MAPK signaling activation. Therefore, irisin may serve as a potential drug for the treatment of patients with ischemic stroke.
Burden of Disease and Cost of Illness of Inflammatory Bowel Diseases in Portugal
Authors: Magro Fernando , Portela Francisco , Lago Paula , Chagas Cristina , Moreira Francisco , Pereira Fábio , Rodrigues Bernardo , Pedrosa Hugo , Correia Luis
Published: June 2022

Background: Inflammatory bowel diseases’ (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods: The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps. Results: In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn’s disease and 40% to ulcerative colitis (UC). Conclusion: This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology.
Differential Gene Expression in Cord Blood of Infants Diagnosed with Cerebral Palsy: A Pilot Analysis of the Beneficial Effects of Antenatal Magnesium Cohort
Authors: Dizon Maria L.V. , deRegnier Raye-Ann O. , Weiner Steven J. , Varner Michael W. , Rouse Dwight J. , Costantine Maged M. , Wapner Ronald J. , Thorp Jr. John M. , Blackwell Sean C. , Ayala Nina K. , Saad Antonio F. , Caritis Steve N. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
Published: June 2022

The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated with MgSO4 or placebo, and controls (newborns who ultimately did not develop CP) treated with MgSO4 or placebo. Those who died after birth were excluded. We found that MgSO4 upregulated expression of SCN5A only in the control group, with no change in gene expression in cord blood of newborns who ultimately developed CP. Regardless of MgSO4 exposure, expression of NPBWR1 and FTO was upregulated in cord blood of newborns who ultimately developed CP compared with controls. These data support that MgSO4 may not exert its neuroprotective effect through changes in gene expression. Moreover, NPBWR1 and FTO may be useful as biomarkers and may suggest new mechanistic pathways to pursue in understanding the pathogenesis of CP. The small number of cases ultimately available for this secondary analysis, with male predominance and mild CP phenotype, is a limitation of the study. In addition, differentially expressed genes were not validated by qRT-PCR.
Sistema de espaços livres e urbanidade: uma proposta de avaliação para a cidade de Araguari (MG)
Authors: Oliveira Lucas Martins de , Queiroga Eugenio Fernandes
Published: June 2022

O trabalho analisa Araguari, cidade média localizada na região do Triângulo Mineiro, Minas Gerais, a partir do estudo do seu sistema de espaços livres de edificação. Avalia-se a urbanidade do sistema de espaços livres na escala da mancha urbana, orientada por três aspectos: centralidade, densidade e conectividade. Entende-se como urbanidade a condição socioespacial em que o espaço livre público é capaz de se oferecer enquanto elemento fundamental do meio físico-social adequado ao uso e à interação das pessoas. Observou-se que a qualidade dos espaços livres em muito se difere nos diferentes contextos da cidade, seja nos aspectos qualitativos, seja na distribuição, evidenciando uma clara disparidade Centro-periferia. No entanto, é possível conferir à cidade um incremento de sua urbanidade a partir do reconhecimento e valorização de seu sistema de espaços livres, tanto na cidade consolidada, quanto nas novas áreas de urbanização.
A integridade na conservação da arquitetura moderna: o caso do viaduto do eixo rodoviário sul em Brasília
Authors: Moura Allana de Deus Peixoto , Lira Flaviana Barreto , Melo Carlos Eduardo Luna de
Published: June 2022

O processo de conservação do patrimônio arquitetônico envolve a análise do bem no decorrer do tempo e tem como objetivo a manutenção dos seus valores culturais. Observa-se, muitas vezes, a existência de conflitos entre as condições de degradação do bem e a manutenção dos seus valores, indicando dificuldades quanto à proposição de ações conservativas que possam gerar um menor impacto possível sobre tais valores. O objetivo do presente trabalho é apresentar os desafios trazidos pela manutenção das condições de integridade dentro do contexto das ações de conservação do patrimônio moderno. Para tanto, discute o caso do viaduto do Eixo Rodoviário Sul em Brasília em relação às intervenções que visaram à sua recuperação após o seu desabamento parcial em 2018, buscando analisar em que medida esse processo de restituição das suas condições de integridade considerou seus atributos e valores patrimoniais. Conclui-se que, para que haja um balizamento das ações de conservação no sentido da manutenção do valor patrimonial, ainda que sejam intervenções em elementos estrututrais, é preciso que os aspectos de significância, autenticidade e integridade sejam considerados e avaliados.
Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial
Authors: Ihl Thomas , Ahmadi Michael , Laumeier Inga , Steinicke Maureen , Ferse Caroline , Klyscz Philipp , Endres Matthias , Hastrup Sidsel , Poppert Holger , Palm Frederick , Kandil Farid I. , Weber Joachim E. , von Weitzel-Mudersbach Paul , Wimmer Martin L.J. , Audebert Heinrich J.
Published: June 2022

Background:

The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes.

Methods:

In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up.

Results:

Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5–43.5); 36.1 after 2 years (95% CI, 13.1–59.7) and 29.6 (95% CI, 2.0–57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03–1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96–1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95–1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up.

Conclusions:

Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01586702.
A Centimeter-Wavelength Snowfall Retrieval Algorithm Using Machine Learning
Authors: King Fraser , Duffy George , Fletcher Christopher G.
Published: June 2022

Remote sensing snowfall retrievals are powerful tools for advancing our understanding of global snow accumulation patterns. However, current satellite-based snowfall retrievals rely on assumptions about snowfall particle shape, size, and distribution that contribute to uncertainty and biases in their estimates. Vertical radar reflectivity profiles provided by the vertically pointing X-band radar (VertiX) instrument in Egbert, Ontario, Canada, are compared with in situ surface snow accumulation measurements from January to March 2012 as a part of the Global Precipitation Measurement (GPM) Cold Season Precipitation Experiment (GCPEx). In this work, we train a random forest (RF) machine learning model on VertiX radar profiles and ERA5 atmospheric temperature estimates to derive a surface snow accumulation regression model. Using event-based training–testing sets, the RF model demonstrates high predictive skill in estimating surface snow accumulation at 5-min intervals with a low mean-square error of approximately 1.8 × 10−3 mm2 when compared with collocated in situ measurements. The machine learning model outperformed other common radar-based snowfall retrievals (Ze–S relationships) that were unable to accurately capture the magnitudes of peaks and troughs in observed snow accumulation. The RF model also displayed consistent skill when applied to unseen data at a separate experimental site in South Korea. An estimate of predictor importance from the RF model reveals that combinations of multiple reflectivity measurement bins in the boundary layer below 2 km were the most significant features in predicting snow accumulation. Nonlinear machine learning–based retrievals like those explored in this work can offer new, important insights into global snow accumulation patterns and overcome traditional challenges resulting from sparse in situ observational networks.
To Warn or Not to Warn: Factors Influencing National Weather Service Warning Meteorologists’ Tornado Warning Decisions
Authors: Kim Jiyoun , Seate Anita Atwell , Liu Brooke F. , Hawblitzel Daniel , Funk Theodore
Published: June 2022

Weather warnings are critical risk communication messages because they have the potential to save lives and property during emergencies. However, making warning decisions is challenging. While there have been significant advances in technological weather forecasting, recent research suggests that social factors, including communication, influence warning meteorologists’ decisions to warn. We examine the roles of both scientific and social factors in predicting warning meteorologists’ decisions to warn on tornadoes. To do so, we conducted a cross-sectional survey of National Weather Service forecasters and members of management in the southern and the central regions of the United States, as well as conducted a retrospective data analysis of cross-sectional survey data from the central region Tornado Warning Improvement Project. Results reveal that dependency on radar velocity couplet and a variety of social factors predicted decisions to warn.
Bilateral Lower Extremity Compartment Syndrome Secondary to COVID-19 Myositis in a Young Vaccinated Woman
Authors: Brod Kate M. , Wohl Jordan , Butts Christopher A. , Reilly Eugene F.
Published: June 2022

Coronavirus disease 2019 (COVID-19) typically manifests with respiratory symptoms and can ultimately progress to severe multiorgan failure. Viral myositis, systemic capillary leak syndrome, and arteriovenous thrombosis are atypical manifestations of COVID-19. We present a case of a 33-year-old woman, fully vaccinated against COVID-19, who developed myositis and shock. She ultimately required bilateral lower extremity fasciotomies secondary to compartment syndrome, presumably from COVID-19 myositis. Although compartment syndrome from COVID-19 myositis has been reported for ocular, hand, and thigh compartment syndromes, this is the first case report showing bilateral lower extremity compartment syndrome secondary to COVID-19 myositis in a fully vaccinated individual. As we learn more about COVID-19 and its extrapulmonary effects, it is imperative to consider all working diagnoses when working up patients. Providers must be aware of extrapulmonary effects of COVID-19, particularly in individuals who might deviate from traditional symptoms.
Recent Levels of Evidence in Otolaryngology Journals
Authors: Chia Clemente , Cheung Priscilla , Wibowo Joshua , Dubrava Adam , Manji Jamil , Paddle Paul
Published: June 2022

Objective:

The development of evidence-based medicine has contributed to improved patient outcomes. This study aims to identify the trends in levels of evidence in otolaryngology journals over time, as represented by the 4 most widely circulated peer-reviewed otolaryngology journals.

Methods:

A review of all articles from 2007, 2010, 2013, 2016, and 2019, in 4 major otolaryngology journals. Data points included journal source, year of publication, country of origin, first author sex, and subspecialty category within otolaryngology. Level of evidence was determined based on the study’s primary research question and was graded on a scale of 1 (strongest) to 4 (weakest) based on the Oxford Centre of Evidence-based Medicine - Levels of Evidence guideline. Comparison of levels of evidence was performed using Kruskal-Wallis analysis of variance for ordinal data.

Results:

About 4297 articles were identified over 12 years. The number of research articles remained consistent over the 12 years of this study. Clinical research increased from 78.6% to 85.1%. Female first authorship increased from 20.3% in 2007 to 31.0% in 2019. Of 3558 articles that constituted clinical research from 2007 to 2019, level 1 studies increased from 0.9% to 3.6%, with level 4 studies remaining stable at an overall rate of 60.3%. Randomized controlled trials remained stable at 4.6% of all studies. Systematic reviews increased from 3.2% to 8.4%.

Conclusion:

This article provides an update on the levels of evidence to allow for an honest self-assessment of otolaryngology as a scientific field.
Balloon Sinus Dilation Versus Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis: Systematic Review and Meta-Analysis
Authors: Sinha Parul , Tharakan Theresa , Payne Spencer , Piccirillo Jay F.
Published: June 2022

Objective:

To determine the efficacy of balloon sinus dilation (BSD) compared to functional endoscopic sinus surgery (FESS) or medical management for chronic rhinosinusitis (CRS).

Methods:

A qualified medical librarian conducted a literature search for relevant publications that evaluate efficacy of BSD. Studies were assessed independently by 2 reviewers for inclusion in the systematic review and meta-analysis.

Results:

From 315 abstracts reviewed, 18 studies were included in qualitative review, and 7 were included in meta-analysis. Quantitative analysis included 4 randomized clinical trials (RCTs) and 3 cohort studies comparing baseline and post-operative Sinonasal Outcome Test (SNOT)—20 scores in BSD and FESS. A meta-analysis restricted to the studies reporting SD for changes from baseline (2 RCTs, 1 cohort) showed the pooled difference in means to be 0.435, less than a clinically meaningful difference of 0.8. A separate sensitivity analysis of the studies including 4 additional studies with imputed values of SD for changes from baseline showed the pooled difference of means to be 0.237 assuming the highest level of correlation ( Corr .8) between the pre- and post-intervention scores.

Conclusions:

There is limited high-quality evidence that assesses the efficacy of BSD versus FESS in the management of CRS patients. To better inform CRS management, future studies should compare BSD with endoscopic sinus surgery, hybrid procedures, and/or medical management alone using validated objective and patient-reported outcome measures.
Evaluation of the Linear Composite Conjecture for Unidimensional IRT Scale for Multidimensional Responses
Authors: Strachan Tyler , Cho Uk Hyun , Ackerman Terry , Chen Shyh-Huei , de la Torre Jimmy , Ip Edward H.
Published: June 2022

The linear composite direction represents, theoretically, where the unidimensional scale would lie within a multidimensional latent space. Using compensatory multidimensional IRT, the linear composite can be derived from the structure of the items and the latent distribution. The purpose of this study was to evaluate the validity of the linear composite conjecture and examine how well a fitted unidimensional IRT model approximates the linear composite direction in a multidimensional latent space. Simulation experiment results overall show that the fitted unidimensional IRT model sufficiently approximates linear composite direction when correlation between bivariate latent variables is positive. When the correlation between bivariate latent variables is negative, instability occurs when the fitted unidimensional IRT model is used to approximate linear composite direction. A real data experiment was also conducted using 20 items from a multiple-choice mathematics test from American College Testing.
Straight and cisgender actors playing queer and trans characters: the views of Australian screen stakeholders
Authors: Cover Rob
Published: June 2022

A concept of visibility frames much scholarship and public writing on LGBTQ+ representation in film and television, and underpins diversity reporting and inclusivity measurement. Although visibility is often depicted as a social good, there is a growing critical interest in asking if there are different kinds of visibility, and how these might be differentially valued. This paper reports insights gained from interviews with Australian stakeholders involved in the production of screen entertainment with LGBTQ+ content. The study found that stakeholders are motivated by to create texts that make LGBTQ+ stories and characters visible. The range of approaches to visibility was, however, nuanced and diverse: some understood any LGBTQ+ representation as valuable, while others discussed visibility in contexts of character depth, anti-stereotyping, and visibility tempered by concepts of human dignity. Although visibility is perceived diversely, it remains a significant lens by which creative artists involved in LGBTQ+ texts understand their work.
Behavior Decision Model With Situation Assessment for Intelligent Vehicles Based on Vehicle-to-Everything Information
Authors: Zhang Runde , Zheng Shaowu , Li Weihua
Published: June 2022

Under the application of cooperative vehicle infrastructure technology, vehicles can drive more safely and efficiently in urban traffic environments. This paper presents a behavior decision model composed of a situation assessment module and decision process module to make a decision on lane selection and velocity control. Different common traffic elements are considered, such as surrounding obstacles, traffic lights, lane lines, and road velocity limits, to ensure the model outputs safe and legal behaviors. A green-wave passage strategy is also proposed to allow vehicles to pass through traffic intersections at a smoother velocity and to improve driving efficiency. To verify the correctness and rationality of the model, a Prescan/Simulink co-simulation platform including multiple common urban driving scenarios is established. The results show that the model can output correct behaviors with safety and legitimacy in different scenarios and realize vehicles meeting at intersections, vehicle-following, queuing at intersections with traffic lights, lane-changing for obstacle avoidance, and so forth. Compared with the general decision model without the green-wave passage strategy, the driving time is reduced by an average of 8.53%, and the standard deviation of the driving velocity is reduced by an average of 65.42%, which means that the model can reduce the variation of velocity and improve driving efficiency. The model has a certain practical application value.
Framework for Quantifying Right-Turn-on-Red Conflicts From Existing Radar-Based Vehicle Detection Infrastructure
Authors: Nassereddine Hiba , Santiago-Chaparro Kelvin R. , Noyce David A.
Published: June 2022

Surrogate safety measures (SSMs) have been used as an alternative to crash-based methods to study road safety. This study proposes a framework to estimate SSMs, such as post encroachment time (PET) and time to collision (TTC) values between right-turn-on-red (RTOR) and through vehicles, and demonstrates the feasibility of using vehicle trajectories obtained from existing radar-based vehicle detection systems to calculate such measures. The framework was implemented by the research team using a software-based approach. The framework presented consists of three stages: first, noise removal and classification of vehicles per lane; second, pairing RTOR vehicles and conflicting-through vehicles; and third calculation of PET and TTC values for each interaction using the radar-based vehicle trajectory dataset. Using video recordings, the interactions between right-turning vehicles and conflicting-through vehicles were documented and key vehicle position timestamps were logged. Logged timestamps enabled the calculation of PET. Video recordings acted as a tool to verify the results of PET calculations based on radar-based vehicle trajectory data. Therefore, the validity of the automated calculation of PET based on radar-based vehicle trajectory data was confirmed using the video recordings from the data collection site. The proposed framework demonstrates the potential to expand the capabilities of existing vehicle detection infrastructure to support proactive safety evaluations at a system level and increase the return on investment on existing vehicle detection technology. The proposed framework can be used in the development of safety models using existing vehicle detection infrastructure based on radar technology without the need for image processing techniques or specialized hardware.
Investigation into the Impact of Weight on Diesel Trucks’ NOx Emissions: An Overweight Case Study
Authors: Farzaneh Reza , Johnson Jeremy , Prozzi Jolanda , Jaikumar Rohit , Venugopal Madhu
Published: June 2022

To build an understanding of the emission contribution, especially nitrogen oxides (NOx) emissions, of many overweight/oversized trucks operating in the Dallas-Fort Worth area, U.S., the North Central Texas Council of Governments commissioned the Texas A&M Transportation Institute to conduct an emission testing study. The study team collected and analyzed data on these vehicles’ activities and emissions characteristics. Vehicle activity data collection was performed using portable activity measurement systems, and exhaust emissions data was measured using two portable emission measurement systems. Using methodologies developed by the Environmental Protection Agency for the MOtor Vehicle Emissions Simulator (MOVES) model, both datasets were processed and expressed as emission rates for three loading scenarios. Researchers observed that, because of the sensitivity of the performance of selective catalytic reduction (SCR) to exhaust temperature, NOx data observed during a test cycle may not result in emission rates that are representative of the real-world operations. The team developed a methodology to adjust the resulting NOx rates for SCR-equipped trucks. The findings of the analysis suggest that the current MOVES opMode equations do not appear to adequately capture the impact of weight on the emission rates of heavy-duty diesel vehicles. The team also found that SCR-equipped trucks can have lower emission rates under heavier loads, especially in higher-speed and higher-power opMode bins, which typically have higher exhaust temperatures. Under normal loads (approximately 55,000 lb), SCR does not seem to provide a NOx emission reduction benefit at speeds under 50 mph compared with exhaust gas recirculation-equipped trucks.
Innovative Strategy Development Approach for Enhancing the Effective Implementation of the International Safety Management (ISM) Code
Authors: Esad Demirci S. M. , Cicek Kadir
Published: June 2022

Maritime transport is a rule-intensive mode of transport. Maritime accidents continue to occur, however, and the catastrophic consequences of such accidents means that maritime transport safety continues to be an important subject. The International Safety Management (ISM) Code is one of the most important steps taken to prevent accidents and enhance shipping safety with the establishment of the safety management system (SMS). However, the important point is not only the establishment of the SMS but also the effective implementation of the ISM Code. To improve the effective implementation of the ISM Code, an innovative strategy development approach has been developed with the integration of Decision-Making Trial and Evaluation Laboratory (DEMATEL) and Theory of Inventive Problem Solving (TRIZ) methodologies. In the study, causal relationships between ISM Code clauses are mainly analyzed with the DEMATEL method. Subsequently, using the results obtained from the analysis of the causal relationships, potential strategies to improve the effective implementation of the ISM Code are presented by using the TRIZ method. The findings of the paper could provide beneficial outcomes for shipping companies and national and international regulatory bodies to enhance maritime transport safety by improving the effectiveness of implementation of the ISM Code.
Virtual Reality and Powerpoint Grocery Store Tours: Equally Effective in Improving Self-efficacy in Randomised Control Trial
Authors: Pilut Jennifer , Hollis James , Lanningham-Foster Lorraine , Pitchford E. Andrew , Litchfield Ruth
Published: June 2022

Purpose

Compare computer-based virtual reality (CBVR) and voice-over PowerPoint (PP) grocery store tours (GST) on adult nutrition literacy (NL) and healthful food purchasing self-efficacy (HFPSE).

Design

Participants (n = 68) recruited from University worksite wellness program and randomly assigned to CBVR or PP (CBVR = 35; PP = 33).

Intervention

Four-week culinary/nutrition education program. Initial three weeks provided identical education for both groups. Week four implemented GST intervention using CBVR or PP.

Measures

NL and HFPSE surveys before, after, and three-months post from the start of program.

Analysis

Intent-to-treat (ITT) analysis with RMANOVA (95% confidence intervals [CI] and effect sizes) to examine change in NL and HFPSE between CBVR and PP groups over 4-week intervention and 3-month retention period.

Results

43 of 68 participants [CBVR (n = 19) and PP (n = 24)] were included in analyses. Both groups significantly improved HFPSE over time (P<.001, CBVR = 46.23% PP = 33.34%), but there were no differences between groups ( P = .21) or group by time interaction ( P = .31). NL did not change for either group ( P = .83, CBVR = 1.11%; PP = .12%) nor were there differences between groups ( P = .07).

Conclusions

CBVR and PP GST significantly improved and maintained higher HFPSE scores.
Alogliptin Induced Stomatitis: An Adverse Drug Event Case Report
Authors: Terry Danielle , Eads Andrea V
Published: June 2022

Background: Dipeptidyl peptidase (DPP)-4 inhibitors are commonly used agents to treat type 2 diabetes mellitus (T2DM). Although generally well tolerated, stomatitis has been previously reported as an adverse event with sitagliptin and linagliptin. Stomatitis with alogliptin has not been reported in post-marketing data to date. Objective: To report a case of suspected drug-induced stomatitis in a patient who received alogliptin for T2DM which resolved upon discontinuation of the offending agent. Summary: A 60-year-old male with T2DM began treatment with a DPP-4 inhibitor, alogliptin. After 4 doses of alogliptin, the patient reported inflammation and irritation along the lateral borders of his tongue, along with open fissures and oral ulcerations on the dorsal surface of the mucosa. He was subsequently diagnosed with stomatitis. Patient discontinued alogliptin and reported improvement in symptoms within 48 hours. Lesions re-epithelialized within 4 weeks after cessation of alogliptin. The Naranjo Algorithm was used to assess causality. The total score was 7, which when interpreted, implicates alogliptin as a “probable” cause of the reaction. Conclusion: A causality assessment determined alogliptin was a “probable” cause of stomatitis experienced by this patient. This adverse effect has not been reported with alogliptin to the authors’ knowledge.
Intranasal Varenicline: Review of a Novel Formulation for the Treatment of Dry Eye Disease
Authors: Zitko Kimberly L. , Ladd Lauren , Dougherty Tyler S.
Published: June 2022

Objective: To examine the literature pertaining to safety and efficacy of intranasal (IN) varenicline for the treatment of dry eye disease (DED). Data Sources: A literature search of PubMed was performed (1985 to January 2022) using the following search terms: varenicline, OC-01, intranasal, and dry eye. Additional data were acquired from references of identified articles, prescribing information, government databases, and manufacturer website. Study Selection/Data Extraction: All relevant English-language studies were included in this review. Data Synthesis: IN varenicline was FDA approved for the treatment of DED in 2021. IN varenicline has demonstrated a statistically significant improvement in outcomes related to basal tear film production as measured by a Schirmer test score (STS) in data from phase 2 and 3 clinical trials. Safety data from these trials have demonstrated that IN varenicline is generally well tolerated with minimal ocular side effects. The most common side effects reported in the trials were sneezing, coughing, along with throat and nasal irritation. Relevance to Patient care and Clinical Practice: Patients suffering from DED have been traditionally treated with ophthalmic preparations; however, many patients struggle with proper administration of ophthalmic products. IN varenicline stimulates nicotinic cholinergic receptors and basal tear film production through the trigeminal parasympathetic nerve pathway (TPP). There is no evidence to support the long-term remission of DED symptoms with IN varenicline as seen with anti-inflammatory modulators. Conclusions: IN varenicline offers an effective and novel approach to management of DED for patients who desire a non-ophthalmic preparation with a favorable side effect profile.