bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine
Authors: Tseng Ssu-Hsueh , Liu Li , Peng Shiwen , Kim Jinhwi , Ferrall Louise , Hung Chien-Fu , Wu T. -C. 
Published: September 2021

AbstractBackgroundHuman Papillomavirus type 16 (HPV16) has been associated with a subset of head and neck cancers. Two HPV encoded oncogenic proteins, E6 and E7, are important for the malignant progression of HPV-associated cancers. A spontaneous HPV16 E6/E7-expressing oral tumor model in human HLA-A2 (AAD) transgenic mice will be important for the development of therapeutic HPV vaccines for the control of HPV-associated head and neck cancers.MethodsIn the current studies, we characterized the HLA-A2 restricted HPV16 E7-specific CD8 + T cell mediated immune responses in the HLA-A2 (AAD) transgenic mice using a therapeutic naked DNA vaccine encoding calreticulin (CRT) linked to a mutated E7(N53S). We also employed oncogenic DNA plasmids that encoded HPV16E6/E7/Luc, NRasG12V, and sleeping beauty transposase for the transfection into the submucosal of oral cavity of the transgenic mice with electroporation to create a spontaneous oral tumor. Furthermore, we characterized the therapeutic antitumor effects of CRT/E7(N53S) DNA vaccine using the spontaneous HPV16 E6/E7-expressing oral tumor model in HLA-A2 (AAD) transgenic mice.ResultsWe found that CRT/E7(N53S) DNA vaccine primarily generated human HPV16 E7 peptide (aa11-20) specific CD8 + T cells, as compared to the wild-type CRT/E7 vaccine, which primarily generated murine H-2Dbrestricted E7 peptide (aa49-57) specific CD8 + T cell responses. We also observed transfection of the oncogenic DNA plasmids with electroporation generated spontaneous oral tumor in all of the injected mice. Additionally, treatment with CRT/E7(N53S) DNA vaccine intramuscularly followed by electroporation resulted in significant antitumor effects against the spontaneous HPV16 E6/E7-expressing oral tumors in HLA-A2 (AAD) transgenic mice.ConclusionsTaken together, the data indicated that the combination of HPV16 E6/E7-expressing DNA, NRasG12VDNA and DNA encoding sleeping beauty transposase is able to generate spontaneous oral tumor in HLA-A2 (AAD) transgenic mice, which can be successfully controlled by treatment with CRT/E7(N53S) DNA vaccine. The translational potential of our studies are discussed.
COVID-19 pandemic: different roles for scientific publications and funding face to epidemiological data—an European, country-based perspective
Authors: Tonacci Alessandro , Genovese Sara , Pioggia Giovanni , Gangemi Sebastiano 
Published: September 2021

AbstractCOVID-19 has represented an unprecedented challenge to be faced also concerning the spread of information, with scientific literature being often the sole source of trustworthy knowledge for the global community. However, a massive waste in research was noticed during pandemic, preventing the scientists to produce totally novel and original results, and the citizenship to have the complete support they needed from science. The present work investigated the relationship between planned funding, research grants, scientific publications and epidemiology in the 27 EU countries, retrieving a significant correlation between scientific publications and COVID-19 cases and deaths, as well as with economic data. Interestingly, planned coronavirus-devoted funds were correlated with lower GDP per capita and higher mortality, leading to the hypothesis for a lack of translation into real funds allowed to the respective country, or for a significant research waste, not transformed into a tangible product or effect. Such results could suggest the need for a different approach in the future concerning the redistribution of research funds in case of COVID-19 relapse or future pandemic events.
Follistatin supplementation induces changes in CDX2 CpG methylation and improves in vitro development of bovine SCNT preimplantation embryos
Authors: Ashry Mohamed , Yang Chunyan , Rajput Sandeep K. , Folger Joseph K. , Knott Jason G. , Smith George W. 
Published: September 2021

AbstractCaudal Type Homeobox 2 (CDX2) is a key regulator of trophectoderm formation and maintenance in preimplantation embryos. We previously demonstrated that supplementation of exogenous follistatin, during in vitro culture of bovine IVF embryos, upregulates CDX2 expression, possibly, via alteration of the methylation status of CDX2 gene. Here, we further investigated the effects of exogenous follistatin supplementation on developmental competence and CDX2 methylation in bovine somatic cell nuclear transfer (SCNT) embryos. SCNT embryos were cultured with or without follistatin for 72h, then transferred into follistatin free media until d7 when blastocysts were collected and subjected to CDX2 gene expression and DNA methylation analysis for CDX2 regulatory regions by bisulfite sequencing. Follistatin supplementation significantly increased both blastocyst development as well as blastocyst CDX2 mRNA expression on d7. Three different CpG rich fragments within the CDX2 regulatory elements; proximal promoter (fragment P1, -1644 to -1180; P2, -305 to +126) and intron 1 (fragment I, + 3030 to + 3710) were identified and selected for bisulfite sequencing analysis. This analysis showed that follistatin treatment induced differential methylation (DM) at specific CpG sites within the analyzed fragments. Follistatin treatment elicited hypomethylation at six CpG sites at positions -1374, -279, -163, -23, +122 and +3558 and hypermethylation at two CpG sites at positions -243 and +20 in promoter region and first intron of CDX2 gene. Motif analysis using MatInspector revealed that differentially methylated CpG sites are putative binding sites for key transcription factors (TFs) known to regulate Cdx2 expression in mouse embryos and embryonic stem cells including OCT1, AP2F, KLF and P53, or TFs that have indirect link to CDX2 regulation including HAND and NRSF. Collectively, results of the present study together with our previous findings in IVF embryos support the hypothesis that alteration of CDX2 methylation is one of the epigenetic mechanisms by which follistatin may regulates CDX2 expression in preimplantation bovine embryos.
Mobile-based interventions for common mental disorders in youth: a systematic evaluation of pediatric health apps
Authors: Domhardt Matthias , Messner Eva-Maria , Eder Anna-Sophia , Engler Sophie , Sander Lasse B. , Baumeister Harald , Terhorst Yannik 
Published: September 2021

AbstractBackgroundThe access to empirically-supported treatments for common mental disorders in children and adolescents is often limited. Mental health apps might extend service supplies, as they are deemed to be cost-efficient, scalable and appealing for youth. However, little is known about the quality of available apps. Therefore, we aimed to systematically evaluate current mobile-based interventions for pediatric anxiety, depression and posttraumatic stress disorder (PTSD).MethodsSystematic searches were conducted inGoogle Play StoreandApple App Storeto identify relevant apps. To be eligible for inclusion, apps needed to be: (1) designed to target either anxiety, depression or PTSD in youth (0–18 years); (2) developed for children, adolescents or caregivers; (3) provided in English or German; (4) operative after download. The quality of eligible apps was assessed with two standardized rating systems (i.e.,Mobile App Rating Scale (MARS)andENLIGHT) independently by two reviewers.ResultsOverall, the searches revealed 3806 apps, with 15 mental health apps (0.39%) fulfilling our inclusion criteria. The mean overall scores suggested a moderate app quality (MARS: M = 3.59, SD = 0.50; ENLIGHT: M = 3.22, SD = 0.73). Moreover, only one app was evaluated in an RCT. The correlation of both rating scales was high (r = .936; p < .001), whereas no significant correlations were found between rating scales and user ratings (p > .05).ConclusionsOur results point to a rather poor overall app quality, and indicate an absence of scientific-driven development and lack of methodologically sound evaluation of apps. Thus, future high-quality research is required, both in terms of theoretically informed intervention development and assessment of mental health apps in RCTs. Furthermore, institutionalized best-practices that provide central information on different aspects of apps (e.g., effectiveness, safety, and data security) for patients, caregivers, stakeholders and mental health professionals are urgently needed.
Chilean validation of the operationalized psychodynamic diagnosis-structure questionnaire (OPD-SQ) for personality structure
Authors: Lorenzini Nicolás , de la Parra G. , Dagnino P. , Gomez-Barris E. , Crempien C. , Ehrenthal J. C. 
Published: September 2021

Abstract
Background
This is the validation of the Operationalized Psychodynamic Diagnosis—Structure Questionnaire (OPD-SQ).

Methods
A clinical sample of 399 adults and a nonclinical general population sample of 50 healthy adults completed measures of depression, attachment, psychiatric symptomatology and distress. Internal consistency and concurrent validity were assessed. Test–retest and Reliable Change Index were also calculated, as was the ability of the OPD-SQ to distinguish between the clinical and general population groups.

Results
High internal consistencies were found; significant differences between clinical and nonclinical samples, and significant associations with psychiatric symptomatology, depression and psychological distress.

Conclusion
The Chilean OPD-SQ has good reliability, and discriminates between clinical and healthy samples.
Attitudes and perceived barriers to firearm safety anticipatory guidance by pediatricians: a statewide perspective
Authors: Ketabchi Bijan , Gittelman Michael A. , Southworth Hayley , Arnold Melissa Wervey , Denny Sarah A. , Pomerantz Wendy J. 
Published: September 2021

Abstract
Background
Firearms are the second leading cause of injury-related death in American children. Safe storage of firearms is associated with a significantly decreased odds of firearm-related death, however more than half of US firearm owners store at least one firearm unlocked or accessible to a minor. While guidance by primary care providers has been shown to improve storage practices, firearm safety counseling occurs infrequently in the primary care setting. The primary objective of this study was to describe pediatricians’ perceived barriers to providing firearm safety education to families in the pediatric primary care setting. Secondary objectives included identifying pediatric provider attitudes and current practices around firearm counseling.

Methods
This was a cross-sectional survey of pediatric primary care providers in Ohio. Participants were recruited from the Ohio AAP email list over a 3-month period. Only pediatric primary care providers in Ohio were included; subspecialists, residents and non-practicing physicians were excluded. Participants completed an anonymous online survey detailing practice patterns around and barriers to providing firearm safety counseling. Three follow-up emails were sent to pediatricians that failed to initially respond. Response frequencies were calculated using Microsoft Excel.

Results
Two hundred eighty-nine pediatricians completed the survey and 149 met inclusion criteria for analysis. One hundred seven (72%) respondents agreed that it is the responsibility of the pediatric primary care provider to discuss safe storage. Counseling, however, occurred infrequently with 119 (80%) of respondents performing firearm safety education at fewer than half of well child visits. The most commonly cited barriers to providing counseling were lack of time during office visits, lack of education and few resources to provide to families. A majority, 82 of pediatric providers (55%), agreed they would counsel more if given additional training, with 110 (74%) conveying they would distribute firearm safety devices to families if these were available in their practice.

Conclusion
Ohio pediatricians agree that it is the responsibility of the primary care provider to discuss firearm safety. However, counseling occurs infrequently in the primary care setting due to a lack of time, provider education and available resources. Improving access to resources for primary care pediatricians will be critical in helping educate families in order to protect their children through improved storage practices.
A practical approach to cluster validation in the energy sector
Authors: Bogensperger Alexander , Fabel Yann 
Published: September 2021

AbstractWith increasing digitization, new opportunities emerge concerning the availability and use of data in the energy sector. A comprehensive literature review shows an abundance in available unsupervised clustering algorithms as well as internal, relative and external cluster validation indices (cvi) to evaluate the results. Yet, the comparison of different clustering results on the same dataset, executed with different algorithms and a specific practical goal in mind still proves scientifically challenging. A large variety of cvi are described and consolidated in commonly used composite indices (e.g. Davies-Bouldin-Index, silhouette-Index, Dunn-Index). Previous works show the challenges surrounding these composite indices since they serve a generalized cluster quality evaluation. However, this does not suit individual clustering goals in many cases. The presented paper introduces the current state of science, existing cluster validation indices and proposes a practical method to combine them to an individual composite index, using Multi Criteria Decision Analysis (mcda). The methodology is applied on two energy economic use cases for clustering load profiles of bidirectional electric vehicles and municipalities.
Asset logging in the energy sector: a scalable blockchain-based data platform
Authors: Djamali Alexander , Dossow Patrick , Hinterstocker Michael , Schellinger Benjamin , Sedlmeir Johannes , Völter Fabiane , Willburger Lukas 
Published: September 2021

AbstractDue to a steeply growing number of energy assets, the increasingly decentralized and segmented energy sector fuels the potential for new digital use cases. In this paper, we focus our attention on the application field of asset logging, which addresses the collection, documentation, and usage of relevant asset data for direct or later verification. We identified a number of promising use cases that so far have not been implemented; supposedly due to the lack of a suitable technical infrastructure. Besides the high degree of complexity associated with various stakeholders and the diversity of assets involved, the main challenge we found in asset logging use cases is to guarantee the tamper-resistance and integrity of the stored data while meeting scalability, addressing cost requirements, and protecting sensitive data. Against this backdrop, we present a blockchain-based platform and argue that it can meet all identified requirements. Our proposed technical solution hierarchically aggregates data in Merkle trees and leverages Merkle proofs for the efficient and privacy-preserving verification of data integrity, thereby ensuring scalability even for highly frequent data logging. By connecting all stakeholders and assets involved on the platform through bilateral and authenticated communication channels and adding a blockchain as a shared foundation of trust, we implement a wide range of asset logging use cases and provide the basis for leveraging platform effects in future use cases that build on verifiable data. Along with the technical aspects of our solution, we discuss the challenges of its practical implementation in the energy sector and the next steps for testing in a regulatory sandbox approach.
Early Changes in Immune Cell Count, Metabolism, and Function Following Sleeve Gastrectomy: A Prospective Human Study
Authors: Lo Tammy , Haridas Renuka S , Rudge Eleanor J M , Chase Robert P , Heshmati Keyvan , Lucey Elizabeth M , Weigl Alison M , Iyoha-Bello Otatade J , Ituah Chelsea O , Benjamin Emily J , McNutt Seth W , Sathe Leena , Farnam Leanna , Raby Benjamin A , Tavakkoli Ali , Croteau-Chonka Damien C , Sheu Eric G 
Published: September 2021

Abstract

Objective
To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG).

Background
LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain.

Methods
Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG.

Results
LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism.

Conclusions
LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery’s effects on immunometabolism and the consequences for host defense and metabolic disease.
A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow
Authors: Rahman Anum , DeYoung Taylor , Cahill Lindsay S. , Yee Yohan , Debebe Sarah K. , Botelho Owen , Seed Mike , Chaturvedi Rajiv R. , Sled John G. 
Published: September 2021

ABSTRACT
In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term and/or have very low disease penetrance. Here, we report the development of a surgically induced mouse model of HLHS that overcomes these limitations. Briefly, we microinjected the fetal left atrium of embryonic day (E)14.5 mice with an embolizing agent under high-frequency ultrasound guidance, which partially blocks blood flow into the left heart and induces hypoplasia. At term (E18.5), all positively embolized mice exhibit retrograde aortic arch flow, non-apex-forming left ventricles and hypoplastic ascending aortas. We thus report the development of the first mouse model of isolated HLHS with a fully penetrant cardiac phenotype and survival to term. Our method allows for the interrogation of previously intractable questions, such as determining the mechanisms of cardiac hypoplasia and fetal abnormalities observed in HLHS, as well as testing of mechanism-based therapies, which are urgently lacking.
ExBoX – a simple Boolean exclusion strategy to drive expression in neurons
Authors: Ubina Teresa , Vahedi-Hunter Tyler , Agnew-Svoboda Will , Wong Wenny , Gupta Akshay , Santhakumar Vijayalakshmi , Riccomagno Martin M. 
Published: September 2021

ABSTRACT
The advent of modern single-cell biology has revealed the striking molecular diversity of cell populations once thought to be more homogeneous. This newly appreciated complexity has made intersectional genetic approaches essential to understanding and probing cellular heterogeneity at the functional level. Here, we build on previous knowledge to develop a simple adeno-associated virus (AAV)-based approach to define specific subpopulations of cells by Boolean exclusion logic (AND NOT). This expression by Boolean exclusion (ExBoX) system encodes for a gene of interest that is turned on by a particular recombinase (Cre or FlpO) and turned off by another. ExBoX allows for the specific transcription of a gene of interest in cells expressing only the activating recombinase, but not in cells expressing both. We show the ability of the ExBoX system to tightly regulate expression of fluorescent reporters in vitro and in vivo, and further demonstrate the adaptability of the system by achieving expression of a variety of virally delivered coding sequences in the mouse brain. This simple strategy will expand the molecular toolkit available for cell- and time-specific gene expression in a variety of systems.
The TPR- and J-domain-containing proteins DJC31 and DJC62 are involved in abiotic stress responses in Arabidopsis thaliana
Authors: Dittmer Sophie , Kleine Tatjana , Schwenkert Serena 
Published: September 2021

ABSTRACT
Molecular chaperones play an important role during the response to different stresses. Since plants are sessile organisms, they need to be able to adapt quickly to different conditions. To do so, plants possess a complex chaperone machinery, composed of HSP70, HSP90, J proteins and other factors. In this study we characterized DJC31 (also known as TPR16) and DJC62 (also known as TPR15) of Arabidopsis thaliana, two J proteins that additionally carry clamp-type tetratricopeptide repeat domains. Using cell fractionation and split GFP, we could show that both proteins are attached to the cytosolic side of the endoplasmic reticulum membrane. Moreover, an interaction with cytosolic HSP70.1 and HSP90.2 could be shown using bimolecular fluorescence complementation. Knockout of both DJC31 and DJC62 caused severe defects in growth and development, which affected almost all organs. Furthermore, it could be shown that the double mutant is more sensitive to osmotic stress and treatment with abscisic acid, but surprisingly exhibited enhanced tolerance to drought. Taken together, these findings indicate that DJC31 and DJC62 might act as important regulators of chaperone-dependent signaling pathways involved in plant development and stress responses.
Parallel mechanisms of visual memory formation across distinct regions of the honey bee brain
Authors: Avalos Arián , Traniello Ian M. , Pérez Claudio Eddie , Giray Tugrul 
Published: September 2021

ABSTRACTVisual learning is vital to the behavioral ecology of the Western honey bee (Apis mellifera). Honey bee workers forage for floral resources, a behavior that requires the learning and long-term memory of visual landmarks, but how these memories are mapped to the brain remains poorly understood. To address this gap in our understanding, we collected bees that successfully learned visual associations in a conditioned aversion paradigm and compared gene expression correlates of memory formation in the mushroom bodies, a higher-order sensory integration center classically thought to contribute to learning, as well as the optic lobes, the primary visual neuropil responsible for sensory transduction of visual information. We quantified expression of CREB and CaMKII, two classical genetic markers of learning, and fen-1, a gene specifically associated with punishment learning in vertebrates. As expected, we found substantial involvement of the mushroom bodies for all three markers but additionally report the involvement of the optic lobes across a similar time course. Our findings imply the molecular involvement of a sensory neuropil during visual associative learning parallel to a higher-order brain region, furthering our understanding of how a tiny brain processes environmental signals.