bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
Authors: Liu Xing-Bo , Yu Guo-Wei , Gao Xin-Yu , Huang Jin-Long , Qin Li-Ting , Ni Hong-Bo , Lyu Chuang 
Published: March 2021

Abstract
Background
DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines.

Methods
In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination.

Results
The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity.

Conclusion
The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate.
NTCP modeling and dose–volume correlations for acute xerostomia and dry eye after whole brain radiation
Authors: Mavroidis Panayiotis , Pearlstein Kevin A. , Moon Dominic H. , Xu Victoria , Royce Trevor J. , Weiner Ashley A. , Shen Colette J. , Marks Lawrence B. , Chera Bhishamjit S. , Das Shiva K. , Wang Kyle 
Published: March 2021

Abstract
Background
Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models.

Methods
Patients received WBRT to 25–40 Gy in 10–20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0–100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman–Kutcher–Burman (LKB) and Relative Seriality (RS) NTCP models.

Results
Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy–V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69–0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy–V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively.

Conclusions
Xerostomia was most associated with parotid V10Gy–V20Gy, and dry eye with lacrimal V10Gy–V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma
Authors: Pisani C. , Vigna L. , Mastroleo F. , Loi G. , Amisano V. , Masini L. , Deantonio L. , Aluffi Valletti P. , Sacchetti G. , Krengli M. 
Published: March 2021

Abstract
Objective
To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT).

Methods and materials
From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, “Marginal recurrence” or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose.

Results
We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6–28.9 cc), while the mean MTVrec was 4.3 cc (1.1–12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61–91%) and 4 recurrences were marginal to MTVpre (1–33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5–69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV).

Conclusion
Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.
A case of vestibular schwannoma mimicking burning mouth syndrome
Authors: Suga Takayuki , Takenoshita Miho , Tu Trang T. H. , Sugawara Takashi , Kirimura Susumu , Toyofuku Akira 
Published: March 2021

Abstract
Background
An oral burning sensation with unidentified cause in patients with preexisting psychosocial conditions is usually diagnosed as burning mouth syndrome. However, unexpected organic lesions may be detected in rare cases.

Case presentation
A 35-year-old woman had chief complaints of a burning sensation and numbness of the right side of the lip and tongue, as well as a dry sensation of the mouth with a taste disturbance of the right side of the tongue. The symptoms were continuous and did not show any daily fluctuations. The symptoms started without any recognizable triggering factor six months before her first visit to our clinic,. No abnormality was detected in her mouth. MRI images revealed an approximately 30 × 30 mm well-defined mass localized in the right cerebropontine angle compressing the trigeminal nerve, which was diagnosed as schwannoma of the right auditory nerve.

Conclusions
It is important for clinicians to consider the possibility of brain tumors in their differential diagnosis of BMS. Although it is not always easy to eliminate all diseases that may cause an oral burning sensation in patients with BMS-like symptoms, more attention and careful examination based on the patient’s psychosomatic background features and other possible causes are needed to rule out organic diseases.
The effect of silica desiccation under different storage conditions on filter-immobilized environmental DNA
Authors: Allison Michael J. , Round Jessica M. , Bergman Lauren C. , Mirabzadeh Ali , Allen Heather , Weir Aron , Helbing Caren C. 
Published: March 2021

Abstract
Objective
Silica gel beads have promise as a non-toxic, cost-effective, portable method for storing environmental DNA (eDNA) immobilized on filter membranes. Consequently, many ecological surveys are turning to silica bead filter desiccation rather than ethanol preservation. However, no systematic evaluation of silica bead storage conditions or duration past 1 week has been published. The present study evaluates the quality of filter-immobilized eDNA desiccated with silica gel under different storage conditions for over a year using targeted quantitative real-time polymerase chain reaction (qPCR)-based assays.

Results
While the detection of relatively abundant eDNA target was stable over 15 months from either ethanol- or silica gel-preserved filters at − 20 and 4 °C, silica gel out-performed ethanol preservation at 23 °C by preventing a progressive decrease in eDNA sample quality. Silica gel filter desiccation preserved low abundance eDNA equally well up to 1 month regardless of storage temperature (18, 4, or − 20 °C). However only storage at − 20 °C prevented a noticeable decrease in detectability at 5 and 12 months. The results indicate that brief storage of eDNA filters with silica gel beads up to 1 month can be successfully accomplished at a range of temperatures. However, longer-term storage should be at − 20 °C to maximize sample integrity.
Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy
Authors: Lodewijk Iris , Nunes Sandra P. , Henrique Rui , Jerónimo Carmen , Dueñas Marta , Paramio Jesús M. 
Published: March 2021

Abstract
Background
Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage.

Main body
Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy.

Conclusion
Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.
Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer
Authors: Mooney Rachael , Abidi Wafa , Batalla-Covello Jennifer , Ngai Hoi Wa , Hyde Caitlyn , Machado Diana , Abdul-Majid Asma , Kang Yanan , Hammad Mohamed , Flores Linda , Copeland Greg , Dellinger Thanh , Han Ernest , Berlin Jacob , Aboody Karen S. 
Published: March 2021

Abstract
Background
Immortalized, clonal HB1.F3.CD21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored.

Methods
To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies.

Results
Here, we report efficient tumor tropism of HB1.F3.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting.

Conclusions
Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.
Spheres of legislation: polarization and most influential nodes in behavioral context
Authors: Phillips Andrew C. , Irfan Mohammad T. , Ostertag-Hill Luca 
Published: March 2021

AbstractGame-theoretic models of influence in networks often assume the network structure to be static. In this paper, we allow the network structure to vary according to the underlying behavioral context. This leads to several interesting questions on two fronts. First, how do we identify different contexts and learn the corresponding network structures using real-world data? We focus on the U.S. Senate and apply unsupervised machine learning techniques, such as fuzzy clustering algorithms and generative models, to identify spheres of legislation as context and learn an influence network for each sphere. Second, how do we analyze these networks to gain an insight into the role played by the spheres of legislation in various interesting constructs like polarization and most influential nodes? To this end, we apply both game-theoretic and social network analysis techniques. In particular, we show that game-theoretic notion of most influential nodes brings out the strategic aspects of interactions like bipartisan grouping, which structural centrality measures fail to capture.
Prior context influences motor brain areas in an auditory oddball task and prefrontal cortex multitasking modelling
Authors: Mugruza-Vassallo Carlos A. , Potter Douglas D. , Tsiora Stamatina , Macfarlane Jennifer A. , Maxwell Adele 
Published: March 2021

AbstractIn this study, the relationship of orienting of attention, motor control and the Stimulus- (SDN) and Goal-Driven Networks (GDN) was explored through an innovative method for fMRI analysis considering all voxels in four experimental conditions: standard target (Goal; G), novel (N), neutral (Z) and noisy target (NG). First, average reaction times (RTs) for each condition were calculated. In the second-level analysis, ‘distracted’ participants, as indicated by slower RTs, evoked brain activations and differences in both hemispheres’ neural networks for selective attention, while the participants, as a whole, demonstrated mainly left cortical and subcortical activations. A context analysis was run in the behaviourally distracted participant group contrasting the trials immediately prior to the G trials, namely one of the Z, N or NG conditions, i.e. Z.G, N.G, NG.G. Results showed different prefrontal activations dependent on prior context in the auditory modality, recruiting between 1 to 10 prefrontal areas. The higher the motor response and influence of the previous novel stimulus, the more prefrontal areas were engaged, which extends the findings of hierarchical studies of prefrontal control of attention and better explains how auditory processing interferes with movement. Also, the current study addressed how subcortical loops and models of previous motor response affected the signal processing of the novel stimulus, when this was presented laterally or simultaneously with the target. This multitasking model could enhance our understanding on how an auditory stimulus is affecting motor responses in a way that is self-induced, by taking into account prior context, as demonstrated in the standard condition and as supported by Pulvinar activations complementing visual findings. Moreover, current BCI works address some multimodal stimulus-driven systems.
Provider perspectives on beta-lactam therapeutic drug monitoring programs in the critically ill: a protocol for a multicenter mixed-methods study
Authors: Barreto Erin F. , Rule Andrew D. , Alshaer Mohammad H. , Roberts Jason A. , Abdul Aziz Mohd Hafiz , Scheetz Marc H. , Mara Kristin C. , Jannetto Paul J. , Gajic Ognjen , O’Horo John C. , Boehmer Kasey R. 
Published: March 2021

Abstract
Background
Beta-lactams (i.e., penicillins, cephalosporins, carbapenems, monobactams) are the most widely used class of antibiotics in critically ill patients. There is substantial interpatient variability in beta-lactam pharmacokinetics which renders their effectiveness and safety largely unpredictable. One strategy to ensure achievement of therapeutic concentrations is drug level testing (“therapeutic drug monitoring”; TDM). While studies have suggested promise with beta-lactam TDM, it is not yet widely available or implemented. This protocol presents a mixed-methods study designed to examine healthcare practitioners’ perspectives on the use and implementation of beta-lactam TDM in the critically ill.

Methods
An explanatory sequential mixed-methods design will be used [QUANT → qual]. First, quantitative data will be collected through a web-based questionnaire directed at clinicians at three academic medical centers at different phases of beta-lactam TDM implementation (not yet implemented, partially implemented, fully implemented). The sampling frame will include providers from a variety of disciplines that interact with drug level testing and interpretation in the critical care environment including pharmacists, intensivists, infectious diseases experts, medical/surgical trainees, and advanced practice providers. Second, approximately 30 individuals will be purposively sampled from survey respondents to conduct in-depth qualitative interviews to explain and expand upon the results from the quantitative strand. Normalization Process Theory and the Consolidated Framework for Implementation Science will be used to guide data analysis.

Discussion
These data will be used to answer two specific questions: “What are ICU practitioners’ perspectives on implementing beta-lactam TDM?” and “What factors contribute to the success of beta-lactam TDM program implementation?” Results of this study will be used to design future implementation strategies for beta-lactam TDM programs in the critically ill.

Trial registration
NCT04755777.
A systematic review of automated journalism scholarship: guidelines and suggestions for future research
Authors: Danzon-Chambaud Samuel 
Published: March 2021

Background: The use of advanced algorithmic techniques is increasingly changing the nature of work for highly trained professionals. In the media industry, one of the technical advancements that often comes under the spotlight is automated journalism, a solution generally understood as the auto generation of journalistic stories through software and algorithms, without any human input except for the initial programming. Methods: In order to conduct a systematic review of existing empirical research on automated journalism, I analysed a range of variables that can account for the semantical, chronological and geographical features of a selection of academic articles as well as their research methods, theoretical backgrounds and fields of inquiry. I then engaged with and critically assessed the meta-data that I obtained to provide researchers with a good understanding of the main debates dominating the field. Results: My findings suggest that the expression “automated journalism” should be called into question, that more attention should be devoted to non-English speaking scholarship, that the collective and individual impacts of the technology on media practitioners should be better documented and that well-established sociological theories such as institutionalism and Bourdieu’s field theory could constitute two adequate frameworks to study automated journalism practices. Conclusions: This systematic literature therefore provides researchers with an overview of the main challenges and debates that are occurring within the field of automated journalism studies. Future studies should, in particular, make use of institutionalism and field theory to explore how automated journalism is impacting the work of media practitioners, which could help unearth common patterns across media organisations.
A Rationale for Imperfect Reporting Standards
Authors: Friedman Henry L. , Hughes John S. , Michaeli Beatrice 
Published: March 2021

The aim of general purpose financial reporting is to provide information that is useful to investors, lenders, and other creditors. With this goal, regulators have tended to mandate increased disclosure. We show that increased mandatory disclosure can weaken a firm’s incentive to acquire and voluntarily disclose private information that is not amenable to inclusion in mandated reports. Specifically, we provide conditions under which a regulator, seeking to maximize the total amount of information provided to investors via both mandatory and voluntary disclosures, would mandate less informative and more conservative financial reports even in the absence of any direct costs of increasing informativeness. This result is robust to allowing the firm to make reports more informative and to imposing a nondisclosure cost or penalty on the firm. The results and comparative statics analysis contribute to our understanding of interactions between mandatory reporting and voluntary disclosure and demonstrate a novel benefit to setting accounting standards that mandate imperfectly informative reports. This paper was accepted by Suraj Srinivasan, accounting.