bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Switch–Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer
Authors: Deblois Geneviève , Tonekaboni Seyed Ali Madani , Grillo Giacomo , Martinez Constanza , Kao Yunchi Ingrid , Tai Felicia , Ettayebi Ilias , Fortier Anne-Marie , Savage Paul , Fedor Alexandra N. , Liu Xiaojing , Guilhamon Paul , Lima-Fernandes Evelyne , Murison Alex , Kuasne Hellen , Ba-alawi Wail , Cescon David W. , Arrowsmith Cheryl H. , De Carvalho Daniel D. , Haibe-Kains Benjamin , Locasale Jason W. , Park Morag , Lupien Mathieu 
Published: June 2020

Abstract

Tumor progression upon treatment arises from preexisting resistant cancer cells and/or adaptation of persister cancer cells committing to an expansion phase. Here, we show that evasion from viral mimicry response allows the growth of taxane-resistant triple-negative breast cancer (TNBC). This is enabled by an epigenetic state adapted to taxane-induced metabolic stress, where DNA hypomethylation over loci enriched in transposable elements (TE) is compensated by large chromatin domains of H3K27me3 to warrant TE repression. This epigenetic state creates a vulnerability to epigenetic therapy against EZH2, the H3K27me3 methyltransferase, which alleviates TE repression in taxane-resistant TNBC, leading to double-stranded RNA production and growth inhibition through viral mimicry response. Collectively, our results illustrate how epigenetic states over TEs promote cancer progression under treatment and can inform about vulnerabilities to epigenetic therapy.

Significance:
Drug-resistant cancer cells represent a major barrier to remission for patients with cancer. Here we show that drug-induced metabolic perturbation and epigenetic states enable evasion from the viral mimicry response induced by chemotherapy in TNBC. These epigenetic states define a vulnerability to epigenetic therapy using EZH2 inhibitors in taxane-resistant TNBC.
See related commentary by Janin and Esteller, p. 1258.
This article is highlighted in the In This Issue feature, p. 1241
Variability of mandible shape in the freshwater glacial relict Eurytemora lacustris (Poppe, 1887) (Copepoda, Calanoida, Temoridae)
Authors: Sługocki Łukasz 
Published: June 2020

Abstract
The mandibles of copepods are used to classify the feeding modes of certain species, because these appendages have specific shapes. The number, shape, location, and structure of the mandibular teeth are traits that are related to the feeding preferences of copepods. Therefore, the mandibles have been used as parameters in order to determine the role of the corresponding species in the trophic network. In this study, we aimed to determine the morphological variability of the mandible shape in a rare calanoid, Eurytemora lacustris (Poppe, 1887). The size of the mandibles of E. lacustris is closely related to its body size; however, considering the proportions of the width of the mandibles to that body size, young individuals have relatively larger mandibles. Despite the large body size of males, the females are characterized by larger mandibles than those of males. The teeth of males were found to be smaller, because of intensive abrasion. Moreover, the season and habitat affected the size of the mandibles and also the values of the edge index (EI). The food conditions in the studied lakes fluctuated within seasons, which led to changes in the shape of the dental crowns. Using this index (EI), E. lacustris was classified as an omnivorous species; however, the range of calculated values varied considerably. We note that the values of the EI decrease along with maturation, which suggests that with increase in age, the copepod becomes more herbivorous; however, this contradicts the paradigm that copepods become omnivorous during maturation. All those morphological differences, furthermore, indicate the high phenotypic plasticity of the species, which was found to be related to maturity, sex, phenology, and the environmental conditions of the habitat.
A multi-year investigation of the Temoridae (Copepoda, Calanoida) assemblage succession within the interplay waters of the northern South China Sea
Authors: Tseng Li-Chun , Wang Yan-Guo , Lian Guang-Shan , Hwang Jiang-Shiou 
Published: June 2020

Abstract
The South China Sea is the largest marginal sea in the world. The northern South China Sea has a complex hydrographic system affected by interplay waters of the Kuroshio Branch Current and the South China Sea waters. To understand the changes in the community structure of the planktonic calanoid copepod family Temoridae in relation to the interplay waters, we collected zooplankton samples in the northern South China Sea from surface waters (0 to 2 m) from November 2001 to January 2007 during 24 research cruises using a standard North Pacific zooplankton net (with a mesh size of 200 μm, a length of 1.8 m, and a mouth diameter of 0.45 m). Among a total of 253 samples, 5 species belonging to 3 genera of Temoridae were identified: Eurytemora pacifica Sato, 1913, Temora discaudata Giesbrecht, 1889, Temora stylifera (Dana, 1849), Temora turbinata (Dana, 1849), and Temoropia mayumbaensis Scott T., 1894. The 3 most abundant species were: T. turbinata (relative abundance, RA: 53.28%; mean density ± standard deviation, MD: 29.33 ± 89.53 ind. m−3), T. stylifera (RA: 36.02%, MD: 19.83 ± 145.22 ind. m−3), and T. discaudata (RA: 7.70%, MD: 4.24 ± 11.82 ind. m−3). The 3 most frequently occurring species were: T. turbinata (occurrence ratio, OR: 52.17%), T. discaudata (OR: 35.18%), and T. stylifera (OR: 9.88%). A noteworthy discovery in our samples was E. pacifica, a marine and brackish water species, collected from 3 stations located near the Kuroshio Branch Current in April 2003. This is the only month when this species was recorded during the investigation period. Variations of dominant species of Temoridae show a clear pattern of seasonal succession. The total abundance was significantly higher in the third quarter (September-November, 116.98 ± 314.49 ind. m−3) than in the fourth quarter (December-February, 24.26 ± 47.72 ind. m−3) (, one-way ANOVA). In general, the present results demonstrate that the assemblages of the Temoridae are very much structured by the water masses of the Kuroshio Current and the South China Sea.
Assessing National Utilization Trends and Outcomes of Robotic and Endoscopic Thyroidectomy in the United States
Authors: Jacobs Daniel , Torabi Sina J. , Gibson Courtney , Rahmati Rahmatullah , Mehra Saral , Judson Benjamin L. 
Published: June 2020

ObjectiveWe aimed to evaluate trends and outcomes of surgical approaches to thyroid surgery. We hypothesized that there have been changes over time in the utilization of approaches to thyroidectomy, including endoscopic, robotic, and open approaches, and that patient outcomes may differ between open surgery and endoscopic or robotic approaches.Study DesignRetrospective analysis.SettingThe National Cancer Database (NCDB) was queried between 2010 and 2016.Subjects and MethodsNational cohort of patients. Descriptive statistics were performed using χ2 test, Mann‐Whitney U test, t test and analysis of variance. To investigate complication rates, patient matching was performed with subsequent analysis using simple and multivariable logistic regressions.ResultsWe identified 217,938 patients within the NCDB. While endoscopic thyroid surgery increased, relatively, in use over time (0.93% to 2.34% of cases in 2010 and 2016, respectively), robotic thyroid surgery started to decline relatively to other approaches from 2013 to 2016 (0.39% to 0.25% of cases, respectively). The endoscopic approach was performed more commonly than the robotic approach within individual facilities that have reported both procedures (P =. 025). Robotic thyroid surgery was associated with increased risk of positive margins (P =. 046), while endoscopic thyroid surgery was associated with a higher rate of unplanned hospital readmission (OR, 1.55; 95% CI, 1.09‐2.22), longer inpatient stays (OR, 1.55; 95% CI, 1.19‐2.02), and higher 90‐day postoperative mortality (OR, 4.45; 95% CI, 1.58‐12.6).ConclusionEndoscopic thyroid surgery has increased in utilization since 2004 but may have worse morbidity and mortality outcomes compared to open surgery.
Long‐Term Otitis Media Outcomes in Infants With Early Tympanostomy Tubes
Authors: Luu Kimberly , Park James , Shaffer Amber D. , Chi David H. 
Published: June 2020

ObjectiveTo review the otologic outcomes of infants who failed the newborn hearing screen (NBHS) and received early tympanostomy tubes for otitis media with effusion (OME).Study DesignRetrospective case series.SettingTertiary care pediatric hospital.Subjects and MethodsConsecutive patients (2007‐2018) who failed an NBHS and required tympanostomy tubes before 6 months of age were included. Variables including hearing loss and otitis media risk factors, episodes of acute otitis media (AOM), number of subsequent tympanostomy tubes, and posttympanostomy tube audiogram results were recorded.ResultsThe cohort included 171 patients. Median age at referral to otolaryngology was 2.7 months. Sensorineural hearing loss (SNHL) was subsequently identified in 22 (12.9%) of infants after resolution of the effusion. The peak incidence of AOM was during the second year of life (1‐1.9 years), with a median of 1 episode. Ninety‐five patients (55.6%) had replacement of tubes, 41 of 171 (24.0%) had 2 or more additional sets of tubes, and long‐term tubes were eventually placed in 8 of 95 (8.4%) patients. Craniofacial anomalies were identified in 43.3% of patients. Tube replacement (hazard ratio, 3.00; 95% CI, 1.95‐4.63; P <. 01, log‐rank) and AOM (β, 1.04; 95% CI, 0.43‐1.65; P =. 04, ordered logistic regression) were more common, and SNHL less common (odds ratio, 0.17; 95% CI, 0.031‐0.61; P <. 01, logistic regression), in children with craniofacial anomalies.ConclusionOME is a common cause of failed NBHS. A notable proportion was subsequently found to have SNHL, reiterating the need for postoperative hearing assessments. Infants meeting indication for early tympanostomy tubes for resolution of OME have a high incidence of recurrent AOM and require subsequent tubes.
Olfactory and Oral Manifestations of COVID‐19: Sex‐Related Symptoms—A Potential Pathway to Early Diagnosis
Authors: Biadsee Ameen , Biadsee Ameer , Kassem Firas , Dagan Or , Masarwa Shchada , Ormianer Zeev 
Published: June 2020

ObjectiveThe coronavirus disease 2019 (COVID‐19) pandemic poses a threat to global health. Early diagnosis is an essential key to limit the outbreak of the virus.Study DesignCase series, study conducted between March 25, 2020, and April 15, 2020.SettingAmbulatory, nonhospitalized patients who were quarantined in a designated hotel for COVID‐19 patients and were recruited by an advertisement at the hotel.Subjects and MethodsIn total, 140 patients participated in a web‐based questionnaire assessing initial symptoms of common viral diseases, olfactory and taste functions, xerostomia, and orofacial pain.ResultsA total of 58 men and 70 women participated. Initial symptoms were cough (59.4%), weakness (47.7%), myalgia (46.9%), fever (42.2%), headache (40.6%), impaired sense of smell (38.3%), impaired sense of taste (32.8%), sore throat (26.6%), runny nose (26.6%), and nasal congestion (22.7%). All symptoms were more frequent among women; however, only runny nose was statistically significant (P =. 018). The most common combination of symptoms was cough and weakness (37.5%). A total of 25.8% reported olfactory and taste dysfunctions in the absence of other symptoms. In a comparison between the sexes, cough and runny nose were the most common combination in women (P =. 018). A total of 38.3% of patients reported olfactory dysfunction as an initial symptom. Anosmia and facial pain were more common among women (P <. 001 and P =. 01, respectively), and 56% of patients reported xerostomia.ConclusionA considerable number of patients presented with olfactory and oral disorders. Interestingly, women presented with a different cluster of symptoms than men, which may suggest a new clinical approach to diagnosing COVID‐19 disease.
Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury
Authors: Iyer Shama R. , Scheiber Amanda L. , Yarowsky Paul , Henn R. Frank , Otsuru Satoru , Lovering Richard M. 
Published: June 2020

Background: Clinical use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) has gained momentum as treatment for muscle injuries. Exosomes, or small cell–derived vesicles, could be helpful if they could deliver the same or better physiological effect without cell transplantation into the muscle. Hypothesis: Local delivery of exosomes derived from PRP (PRP-exos) or MSCs (MSC-exos) to injured muscles hastens recovery of contractile function. Study Design: Controlled laboratory study. Methods: In a rat model, platelets were isolated from blood, and MSCs were isolated from bone marrow and expanded in culture; exosomes from both were isolated through ultracentrifugation. The tibialis anterior muscles were injured in vivo using maximal lengthening contractions. Muscles were injected with PRP-exos or MSC-exos (immediately after injury and 5 and 10 days after injury); controls received an equal volume of saline. Histological and biochemical analysis was performed on tissues for all groups. Results: Injury resulted in a significant loss of maximal isometric torque (66% ± 3%) that gradually recovered over 2 weeks. Both PRP-exos and MSC-exos accelerated recovery, with similar faster recovery of contractile function over the saline-treated group at 5, 10, and 15 days after injury ( P < .001). A significant increase in centrally nucleated fibers was seen with both types of exosome groups by day 15 ( P < .01). Genes involved in skeletal muscle regeneration were modulated by different exosomes. Muscles treated with PRP-exos had increased expression of Myogenin gene ( P < .05), whereas muscles treated with MSC-exos had reduced expression of TGF-β ( P < .05) at 10 days after muscle injury. Conclusion: Exosomes derived from PRP or MSCs can facilitate recovery after a muscle strain injury in a small-animal model likely because of factors that can modulate inflammation, fibrosis, and myogenesis. Clinical Relevance: Given their small size, low immunogenicity, and ease with which they can be obtained, exosomes could represent a novel therapy for many orthopaedic ailments.
A real-world data approach to determine the optimal dosing strategy for pembrolizumab
Authors: Jang Ashley , Nakashima Lynne , Ng Tonya , Fung Mayo , Jiwani Samarah , Schaff Kimberly , Suess Jennifer , Goncalves Randy , Jang Dennis , Kuik Kimberly , Labelle Sylvie , Pow Alison 
Published: June 2020

Introduction Cancer drug therapy costs continue to rise and threaten the sustainability of Canada’s public healthcare system. Previous studies have calculated potential savings utilizing different dosing regimens of cancer treatments. Our objectives were to determine the financial impact of drug wastage and to explore cost-effective dosing regimens for pembrolizumab. Methods This was a retrospective study reviewing data for non-small cell lung cancer and melanoma patients at all six BC Cancer Regional Centres during fiscal years 2017 and 2018. Pembrolizumab waste amounts recorded in pharmacy wastage logs were totalled. Estimates of the number of vials used were compared between vial sharing and non-vial sharing practices to determine the cost differences. Costs for dosing regimens used during fiscal years 2017 and 2018 were compared to 2 mg/kg weight-based dosing (to a maximum of 200 mg), 2 mg/kg dosing rounding down within 5% and 10%, and flat dosing of 200 mg. Results There were a total of 202 non-small cell lung cancer and 182 melanoma patients with 2948 doses dispensed. Documented wastage was valued at $1,829,047.44 (8.65%) and across all six centres, vial sharing could reduce costs by $3,207,600.00 using the 100 mg vials. Compared to fiscal years 2017 and 2018, 2 mg/kg dosing (to a maximum of 200 mg) was the most cost-effective, decreasing costs by $222,719.20; flat dosing of 200 mg was the most expensive, increasing costs by $6,625,260.40. Conclusions Having smaller vial sizes, practicing vial sharing, and using weight-based dosing all improve cost savings. Further investigations on the allocation of resources to optimize drug use and minimize wastage are needed.
High-altitude mountain telemedicine
Authors: Martinelli Massimo , Moroni Davide , Bastiani Luca , Mrakic-Sposta Simona , Giardini Guido , Pratali Lorenza 
Published: June 2020

Introduction An innovative teleconsultation platform has been designed, developed and validated between summer 2017 and winter 2018, in five mountain huts and in three remote outpatient clinical centres of the Italian region Valle d’Aosta of the Mont Blanc massif area. Methods An ad-hoc videoconference system was developed within the framework of the e-Rés@MONT (Interreg ALCOTRA) European project, to tackle general health problems and high-altitude diseases (such as acute mountain sickness, high-altitude pulmonary and cerebral oedema). The system allows for contacting physicians at the main hospital in Aosta to perform a specific diagnosis and to give specific advice and therapy to the patients in an extreme environment out-hospital setting. At an altitude between 1500–3500 m, five trained nurses performed clinical evaluations (anamnesis, blood pressure, heart rate, oxygen saturation), electrocardiographic and echography monitoring on both tourists and residents as necessary; all of the collected data were sent to the physicians in Aosta. Results A total of 702 teleconsultation cases were performed: 333 dismissed (47%), 356 observed (51%) and 13 immediate interventions (2%). In 30 cases the physicians decided there was no need for helicopter and ambulance rescue intervention and hospital admissions. The main physiological measures, the classified pathologies, the severe cases and the cost savings are described in this article. Discussion The e-Rés@MONT teleconsultation platform has been discussed in terms of treated cases, feasibility, proactivity in reducing complexities, direct and indirect advantages, and diagnostics help; moreover, general and specific pros and cons have been debated, and future steps have been exposed.
Phonetic drift reveals interconnected phonological representations in simultaneous bilinguals: A case study of English and Czech stop consonants
Authors: Podlipský Václav Jonáš , Šimáčková Šárka , Chládková Kateřina 
Published: June 2020

Purpose: The interconnectedness of phonological categories between the two languages of early bilinguals has previously been explored using single-probe speech production and perception data. Our goal was to tap into bilingual phonological representations in another way, namely via monitoring instances of phonetic drift due to changes in language exposure. Design: We report a case study of two teenage English–Czech simultaneous bilinguals who live in Canada and spend summers in Czechia (Czech Republic). Voice onset time (VOT) of word-initial voiced and voiceless stops was measured upon the bilinguals’ arrival to and before their departure from a two-month stay in Czechia. Data and Analysis: Each bilingual read the same set of 71 Czech and 58 English stop-initial target words (and additional fillers) at each time of measurement. The measured VOT values were submitted to linear mixed effects models, assessing the effects of target language, measurement time, and underlying voicing. Findings/Conclusions: After the immersion in a Czech-speaking environment, for both speakers the count of voiced stops realized as prevoiced (i.e., having negative VOT) increased and the measured VOT of voiced stops (appearing different for English and Czech initially) drifted towards more negative (more Czech-like) values in both languages, while no change was detected for the voiceless stops of either English (aspirated) or Czech (unaspirated). The results suggest that the bilinguals maintain three-way VOT distinctions, differentiating voiceless aspirated (English), voiceless unaspirated (Czech), and voiced (English–Czech) stops, with connected bilingual representations of the voiced categories. Originality: Data on phonetic drift in simultaneous bilinguals proficient in their two languages have not previously been published. Significance/Implications: We show that observing phonetic shifts due to changes in the ambient linguistic environment can be revealing about the organization of phonological space in simultaneous bilinguals.
The virtual fracture clinic improves quality of care for patients with hand and wrist injuries: an assessment of 3709 patients
Authors: Little Max , Huntley Daniel , Morris James , Jozsa Felix , Hardman John , Anakwe Raymond E. 
Published: June 2020

Fracture clinic services are under significant pressures to meet patients' expectations of a high-quality service. The virtual fracture clinic has shown early promise in helping to reduce such pressures. We used the virtual fracture clinic for hand and wrist injuries treated in the orthopaedic fracture clinic and used key quality indicators to measure improvement. Over the first 21 months, key patient outcome measures and satisfaction scores for patients discharged from the virtual fracture clinic with education to self-care were excellent. Our results show that a virtual fracture clinic model can be applied to provide high-quality care for hand and wrist injuries. The main advantage of the virtual fracture clinic is its ability to direct patients to the right person for timely treatment. We conclude from our 21-month experience that this model of care allows safe, effective, patient-centred, efficient and equitable care to the patients with hand and wrist fractures. Level of evidence: IV
The Role of Home Fungal Exposure in Allergic Fungal Rhinosinusitis
Authors: Rowan Nicholas R. , Storck Kristina A. , Schlosser Rodney J. , Soler Zachary M. 
Published: June 2020

Background Allergic fungal rhinosinusitis (AFRS) is disproportionately identified in patients of low socioeconomic status living in warm, humid climates, and is thought to occur in response to environmental fungal species. Objective We hypothesized that micro-geographic differences in fungal exposure contribute to the pathogenesis of AFRS, and compared home fungal exposure of patients with AFRS to normative data and controls. Methods Comprehensive prospective enrollment and data capture was completed in 70 patients. Patients with AFRS were compared to a control population with chronic rhinosinusitis with nasal polyposis (CRSwNP) and comorbid atopy. Comprehensive demographics, 22-item sino-nasal outcomes test (SNOT-22) questionnaires, and endoscopy scores were compiled. Using a test strip collection system, a home fungal assessment was completed for each patient, along with detailed questions related to home condition. Results Patients with AFRS were more likely to be younger (p<.001), African American (p<.001), from a lower income bracket (p < .012), and less likely to own their home (p < .001). There were no differences in prior surgeries (p=.432), endoscopy scores (p = .409) or SNOT-22 scores (p = .110) between the groups. There were no differences in overall fungal counts between patients with AFRS and controls (p = .981). AFRS patients had a higher prevalence of Basidiospores than controls (p = .034). Conclusion This study failed to detect differences in total home fungal exposure levels between those with AFRS and atopic CRSwNP, despite differences in socioeconomic status. This suggests that absolute fungal levels may not be the primary driver in development of AFRS, or that the fungal detection strategies utilized were not representative of patients’ overall fungal exposure.