bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Authors: Verusingam Nalini Devi , Chen Yi-Chen , Lin Heng-Fu , Liu Chao-Yu , Lee Ming-Cheng , Lu Kai-Hsi , Cheong Soon-Keng , Han-Kiat Ong Alan , Chiou Shih-Hwa , Wang Mong-Lien 
Published: October 2020

Background:
Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance.

Methods:
OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot.

Results:
OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity.

Conclusion:
We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.
Reverse expression of α2,6-sialic acid ratios on IgG, IgM, and IgG/IgM autoantibodies correlates with mouse arthritis and rheumatoid arthritis disease activity
Authors: Liou Lieh-Bang , Huang Che-Ching 
Published: October 2020

Background:
Sialic acids (SIAs), for example, α2,6-SIAs, can link to conserved N-glycans of immunoglobulin G (IgG). In this study, we investigated the correlation between α2,6-SIA on IgG and IgM and the disease activity of arthritis and rheumatoid arthritis (RA) in mice.

Methods:
We measured α2,6-SIA levels in IgGs and IgMs in collagen-induced arthritis (CIA). Additionally, α2,6-SIA levels in rheumatoid factors (RFs) and anti–cyclic citrullinated peptide (anti-CCP) antibodies in RA patients were measured. Correlations between α2,6-SIA on Igs and CIA were analyzed and also in RA patients by utilizing the disease activity score 28 (DAS28). The ability to differentiate RA progression by Ig and autoantibody α2,6-SIA levels was examined.

Results:
In CIA mice, plasma IgG-α2,6-SIA/IgG ratios decreased, whereas plasma IgM-α2,6-SIA/IgM ratios increased. Moreover, arthritis was not observed in collagen-injected mice with decreased IgG-α2,6-SIA/IgG ratios and without increased IgM-α2,6-SIA/IgM ratios. Isolated IgG-α2,6-SIA/IgG ratios displayed a significant inverse correlation with DAS28 scores (r = –0.383, p = 0.037). In contrast, isolated IgM-α2,6-SIA/IgM ratios correlated positively with DAS28 (r = 0.351, p = 0.009). Isolated IgG-anti-CCP-α2,6-SIA/plasma IgG-anti-CCP ratios were differentiated into either the remission (higher ratios) or the nonremission (lower ratios) category (p = 0.061), which is similar to the pattern for C-reactive protein (CRP) (p = 0.041) but different from that for the erythrocyte sedimentation rate (ESR) (p = 0.421). Using multiple linear regression analysis, plasma IgMRF-α2,6-SIA/IgMRF ratios displayed a correlation with DAS28 (p = 0.006), which was also observed in the ESR (p = 0.005), but was different from that for CRP (p = 0.222).

Conclusion:
Concurrent reverse expression of α2,6-SIA ratios on IgM and IgG correlated with the occurrence of CIA and RA disease activity. Thus, α2,6-SIA ratios on IgG-anti-CCP antibodies and IgMRF are potential markers for evaluating RA disease activities.
‘Doc, will I ever eat steak again?’: diagnosis and management of alpha-gal syndrome
Authors: Patel Chirag , Iweala Onyinye I. 
Published: October 2020

Purpose of review
Alpha-gal syndrome encompasses a constellation of symptoms associated with immune-mediated hypersensitivity responses to galactose-alpha-1,3-galactose (alpha-gal). The purpose of this review is to discuss our current understanding of the etiology, clinical symptoms, natural history, epidemiology, and management of alpha-gal syndrome.

Recent findings
Sensitization to alpha-gal is associated with bites from ectoparasites like the lone star tick Amblyomma americanum. Allergic reactions in alpha-gal syndrome are often delayed and inconsistent. The magnitude of the allergic response depends on co-factors like exercise and alcohol consumption and the amount of alpha-gal and fat present in the food. Assaying alpha-gal-specific IgE in the serum is the primary diagnostic test used to confirm the allergy. Long-term management of the condition involves avoidance of both mammalian food products and tick bites.

Summary
Alpha-gal syndrome disrupts the current paradigm for understanding food allergy. Exposure to an ectoparasite is critical for the development of specific IgE antibodies underlying sensitization, and allergic reactions depend on the activation of mast cells and basophils sensitized with IgE against a carbohydrate rather than a protein. Research in this field may lead to the development of improved diagnostic and therapeutic tools that can revolutionize the management of patients with alpha-gal syndrome.
Implementing a Nurse Discharge Navigator
Authors: Weeks Karen , Kile Debbie , Garber Jeannie 
Published: October 2020

Purpose/Objectives:
The purpose of this quality improvement project was to evaluate the impact of a nurse discharge navigator on reducing 30-day readmissions for the heart failure and sepsis populations.

Primary Practice Setting:
The 238-bed community hospital in central Virginia is part of a health care system that encompasses 13 acute care facilities.

Methodology and Sample:
The aim of this project was to identify, implement, and evaluate the transition of care of high-risk readmission patients from January 2019 to April 2019. Inclusion criteria included patients who were 55 years and older, English speaking, diagnosed with heart failure and/or sepsis, discharged to home with or without home health, and/or consults received from case management and social services. Forty-one potential participants were identified with 28 consented. Readmission data were collected pre- and postintervention. The pre-/postanalysis consisted of descriptive statistics, readmission rates, and cost avoidance.

Results:
Out of the 28 participants, 7 participants were readmitted within 30 days. The heart failure readmission rates during the project implementation were as follows: January 24.05%, February 20%, March 19.75%, and April 11.11%. After the project completion the readmission rates were 22.97% for May and 26.03% for June, respectively. The potential cost avoidance with sustained gain from the project is $405,316.00.

Implications for Case Management Practice:
This project demonstrated that a discharge navigator had an effect on 30-day readmissions for high-risk heart failure and sepsis populations, as evident by a steady decline in overall heart failure readmission rate during project implementation. The sepsis population needs further research. The discharge navigator project added to the body of knowledge for comprehensive discharge planning, coordination, and education that is needed for these types of patient populations that have a great deal of medical complexity.
Dissemination and Implementation Science in Plastic and Reconstructive Surgery: Perfecting, Protecting, and Promoting the Innovation That Defines Our Specialty
Authors: Dengler Jana , Padovano William M. , Davidge Kristen , McKay Virginia , Yee Andrew , Mackinnon Susan E. 
Published: October 2020

Summary:
Plastic and reconstructive surgery has an illustrious history of innovation. The advancement, if not the survival, of the specialty depends on the continual development and improvement of procedures, practices, and technologies. It follows that the safe adoption of innovation into clinical practice is also paramount. Traditionally, adoption has relied on the diffusion of new knowledge, which is a consistent but slow and passive process. The emerging field of dissemination and implementation science promises to expedite the spread and adoption of evidence-based interventions into clinical practice. The field is increasingly recognized as an important function of academia and is a growing priority for major health-related funding institutions. The authors discuss the contemporary challenges of the safe implementation and dissemination of new innovations in plastic and reconstructive surgery, and call on their colleagues to engage in this growing field of dissemination and implementation science.
Infections after anti-CD19 chimeric antigen receptor T-cell therapy for hematologic malignancies: timeline, prevention, and uncertainties
Authors: Haidar Ghady , Garner Will , Hill Joshua A. 
Published: October 2020

Purpose of review
Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes.

Recent findings
Infections occur in 23–42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0–30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon.

Summary
Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
The why and how of maintaining hydration during cancer therapy
Authors: Hwa Yi L. , Kull Michelle R. 
Published: October 2020

Purpose of reviewTo provide an overview of the role hydration plays in the oncology population while providing a synopsis of recent scientifically relevant published practice advancements.Recent findingsDehydration causes substantial symptom burden in cancer patients, secondary to both disease process and treatment complications. Maintaining fluid and electrolytes balance is the key to hydration therapy. When oral intake is diminished, artificial hydration can be delivered via enteral, intravenous and subcutaneous routes. Use of artificial hydration in end-of-life care for cancer patients remains a highly debated topic with unclear benefits and lack of established standards. A holistic approach is required in the decision-making process.SummaryMaintaining adequate hydration is important in patients receiving cancer therapy. Challenges exist, secondary to limited clinical guidelines of hydration in patients with advanced cancer. Artificial hydration may be indicated for selected patients at the end of life if used on an individualized basis as medical treatment.
Intraoperative Neuromonitoring of Blink Reflex During Posterior Fossa Surgeries and Its Correlation With Clinical Outcome
Authors: Aydinlar Elif Ilgaz , Kocak Muge , Soykam Huseyin O. , Mat Beril , Dikmen Pinar Y. , Sezerman Osman Ugur , Elmaci İlhan , Pamir Mustafa Necmettin 
Published: October 2020

Purpose:
Blink reflex (BR) under general anesthesia as an intraoperative neuromonitoring method was used to monitor facial nerves in few studies. This study aimed to test the utility of intraoperative BR during cerebellopontine angle and skull base surgeries, assess its prognostic value for facial nerve functions, and compare it with facial corticobulbar motor evoked potentials (CoMEPs).

Methods:
Blink reflex and facial CoMEPs were recorded from 40 patients undergoing skull base surgeries. Subdermal needles were placed in the supraorbital notch for stimulation and in the orbicularis oculi muscle for recording the BR. A double train of 20 to 40 V intensity with an intertrain interval of 40 to 60 milliseconds, an interstimulus interval of 2.5 milliseconds, and a stimulus duration of 0.5 milliseconds were applied. Facial nerve functions were assessed with the House–Brackmann grading system in the postoperative day 1 and third-month period and correlated with intraoperative BR and CoMEPs measurements.

Results:
Of 40 patients, BR was recordable on the affected side in 32 (80%) and contralateral side in 35 (87.5%) patients. According to our statistical results, BR had a slightly better sensitivity than facial CoMEPs in predicting impairment of facial nerve functions for both postoperative and third-month time points. Blink reflex showed better accuracy for predicting postoperative nerve functions, whereas CoMEPs correlated better in predicting third-month outcome.

Conclusions:
We suggest that BR is a valuable intraoperative neuromonitoring method that can be used in addition to facial CoMEPs during skull base surgeries to assess real-time facial nerve integrity and predict prognosis.
Silencing NADPH-Cytochrome P450 reductase affects imidacloprid susceptibility, fecundity, and embryonic development inLeptinotarsa decemlineata
Authors: Moural Timothy W. , Ban Liping , Hernandez Jonathan A. , Wu Meixiang , Zhao Chaoyang , Palli Subba R. , Alyokhin Andrei , Zhu Fang 
Published: October 2020

ABSTRACTThe Colorado potato beetle (CPB) is a prominent insect pest of potatoes, tomatoes and eggplants all over the world, however, the management of CPB remains a challenging task for more than one hundred years. We have successfully developed bacteria-expressed dsRNA-mediated feeding RNA interference (RNAi) approach in our previous study. A critical step towards field management of CPB via feeding RNAi is to identify effective and environmentally safe target genes. NADPH-Cytochrome P450 reductase (CPR) plays a central role in cytochrome P450 action. The full lengthLeptinotarsa decemlineataCPR (LdCPR) cDNA was isolated from an imidacloprid resistant population. TheLdCPRgene was ubiquitously expressed in all stages tested but showed an increase in expression during the early stage of embryonic development. The bacteria-expressed dsRNA-mediated feeding RNAi ofLdCPRin adults caused systemic knock down expression of the gene coding forLdCPRin both adults and their eggs. Suppression ofLdCPRexpression increased susceptibility of imidacloprid in resistant beetles, as well as a significant decrease of fecundity in female beetles (29% less eggs/day) and the hatching rate (47%) of their eggs. These data suggest thatLdCPRplays important roles in insecticide detoxification and biosynthetic pathways of endogenous compounds and may serve as an essential target to control CPB.HIGHLIGHTSHigh expression ofLdCPRwas observed in the egg stage.Silencing ofLdCPRreduced the CPR enzymatic activities.LdCPRknockdown increased imidacloprid susceptibility.LdCPRknockdown decreased the fecundity and enhanced embryonic lethality.
mir-218 modulates ARF6 expression and inhibits pancreatic ductal adenocarcinoma invasion
Authors: Rheinheimer Brenna A. , Heimark Ronald L 
Published: October 2020

AbstractBackgroundPancreatic ductal adenocarcinoma is an extremely malignant disease with the majority of patients having metastatic disease upon diagnosis. Recently, it was shown the SLIT2 plays a regulatory role in melanoma invasion through the control of invadopodia. Therefore, we sought to determine the mechanism behind miR-218 inhibition of pancreatic cancer invasion.Methodsmir-218 target genes were discovered using three miRNA target prediction websites. Modulation of mir-218 target ARF6 was determined by transfection with antagomirs and mimics to mir-218. Pancreatic cancer migration and invasion were measured using Boyden chamber assays. Invasion was further measured using matrix degradation assays.ResultsWe found that mir-218 modulates ARF6 RNA and protein expression in pancreatic cancer. mir-218 did not inhibit pancreatic cancer cell migration, but did inhibit invasion. mir-218 did not affect the formation of invadopodia in pancreatic cancer cells, but did inhibit the total area of matrix degradation caused by functional invadopodia.ConclusionsThis work suggests that miR-218 is a suppressor of pancreatic ductal adenocarcinoma invasion through a pathway that regulates invadopodia maturation.
Time-course single-cell RNA sequencing reveals transcriptional dynamics and heterogeneity of limbal stem cells derived from human pluripotent stem cells
Authors: Sun Changbin , Wang Hailun , Ma Qiwang , Chen Chao , Yue Jianhui , Li Bo , Zhang Xi 
Published: October 2020

AbstractHuman pluripotent stem cell-derived limbal stem cells (hPSC-derived LSCs) provide a promising cell source for corneal transplants and ocular surface reconstruction. Although recent efforts in the identification of LSC markers have increased our understanding of the biology of LSCs, the lack of knowledge of the developmental origin, cell fate determination, and identity of human LSCs hindered the establishment of differentiation protocols for hPSC-derived LSCs and hold back their clinical application. Here, we performed a time-course single-cell RNA-seq to investigate transcriptional heterogeneity and expression changes of LSCs derived from human embryonic stem cells. Based on current protocol, expression heterogeneity of reported LSC markers were identified in subpopulations of differentiated cells. EMT has been shown to occur during differentiation process, which could possibly result in generation of untargeted cells. Pseudotime trajectory analysis revealed transcriptional changes and signatures of commitment of hPSCs-derived LSCs and their progeny - the transit amplifying cells. Furthermore, several new makers of LSCs were identified, which could facilitate elucidating the identity and developmental origin of human LSCsin vivo.
Distinct higher-order representations of natural sounds in human and ferret auditory cortex
Authors: Landemard Agnès , Bimbard Célian , Demené Charlie , Shamma Shihab , Norman-Haignere Sam , Boubenec Yves 
Published: October 2020

AbstractLittle is known about how neural representations of natural sounds differ across species. For example, speech and music play a unique role in human hearing, yet it is unclear how auditory representations of speech and music differ between humans and other animals. Using functional Ultrasound imaging, we measured responses in ferrets to a set of natural and spectrotemporally-matched synthetic sounds previously tested in humans. Ferrets showed similar lower-level frequency and modulation tuning to that observed in humans. But while humans showed prominent selectivity for natural vs. synthetic speech and music in non-primary regions, ferret responses to natural and synthetic sounds were closely matched throughout primary and non-primary auditory cortex, even when tested with ferret vocalizations. This finding reveals that auditory representations in humans and ferrets diverge sharply at late stages of cortical processing, potentially driven by higher-order processing demands in speech and music.
Simulating rainfall IDF curve for flood warnings in the Ca Mau coastal area under the impacts of climate change
Authors: Dang Truong An 
Published: October 2020

Purpose
The purpose of this study is to evaluate the rainfall intensities and their limits for durations from 0.25 to 8 h with return periods from 2 to 100 years for Ca Mau City in Vietnam.

Design/methodology/approach
First, the quality of the historical rainfall data series in 44 years (1975–2018) at Ca Mau station was assessed using the standard normal homogeneity test and the Pettitt test. Second, the appraised rainfall data series are used to establish the rainfall intensity-duration-frequency curve for the study area.

Findings
Based on the findings, a two-year return period, the extreme rainfall intensities (ERIs) ranged from 9.1 mm/h for 8 h rainstorms to 91.2 mm/h for 0.25 h. At a 100-year return period, the ERIs ranged from 18.4 mm/h for 8 h rainstorms to 185.8 mm/h for 0.25 h. The results also show that the narrowest uncertainty level between the lower and upper limits recorded 1.6 mm at 8 h for the two-year return period while the widest range is at 42.5 mm at 0.25 h for the 100-year return period. In general, the possibility of high-intensity rainfall values compared to the extreme rainfall intensities is approximately 2.0% at the 100-year return period.

Originality/value
The results of the rainfall IDF curves can provide useful information for policymakers to make the right decisions in controlling and minimizing flooding in the study area.
Exploring willingness to share in peer-to-peer access-based hospitality markets: the effect of roles performed and sharing intensity
Authors: Teixeira Otávio Ferreira Borges , Caldieraro Fabio , Medeiros Amanda Cristina 
Published: October 2020

Purpose
This study aims to examine the effect of individuals’ roles, as providers or consumers, and sharing intensity on willingness to participate in access-based hospitality markets.

Design/methodology/approach
The research draws from the theories of psychological ownership and prospect theory to examine how individuals’ roles and sharing intensity affect willingness to share an accommodation. Two behavioral experiments test the proposed hypotheses and fundament the main conclusions.

Findings
The results show that providers (consumers) desire more (less) intensive sharing. This paper also finds a significant difference between consumers’ willingness to pay and providers’ willingness to accept, creating a seesaw dilemma that limits the likelihood of closing a sharing agreement. Based on the findings, strategies to improve the likelihood of transactions among parties are suggested.

Practical implications
The research provides guidelines to stimulate peer-to-peer hospitality transactions. It suggests improving communication to highlight consumers’ perceptions of effectance and feeling of “home,” as well as providers’ mental imageries of ownership. It also recommends systematizing accommodation attributes based on expected sharing experiences and the prospection of users who welcome high sharing intensity.

Originality/value
In contrast to other studies of peer-to-peer accommodation sharing, this paper explores the roles of providers and consumers simultaneously and analyze sharing intensity as a critical factor. This study finds that providers may welcome more intensive sharing, and links this outcome to an unusual negative relationship between psychological ownership and the endowment effect.