bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid allele-specific ChIP-seq analysis identifies variation in brassinosteroid-responsive transcription factor binding linked to traits in maize
Authors: Hartwig Thomas , Banf Michael , Prietsch Gisele Passaia , Zhu Jia-Ying , Mora-Ramírez Isabel , Schippers Jos H. M. , Snodgrass Samantha J. , Seetharam Arun S. , Huettel Bruno , Kolkman Judith M. , Yang Jinliang , Engelhorn Julia , Wang Zhi-Yong
Published: May 2023

Background

Genetic variation in regulatory sequences that alter transcription factor (TF) binding is a major cause of phenotypic diversity. Brassinosteroid is a growth hormone that has major effects on plant phenotypes. Genetic variation in brassinosteroid-responsive cis-elements likely contributes to trait variation. Pinpointing such regulatory variations and quantitative genomic analysis of the variation in TF-target binding, however, remains challenging. How variation in transcriptional targets of signaling pathways such as the brassinosteroid pathway contributes to phenotypic variation is an important question to be investigated with innovative approaches.

Results

Here, we use a hybrid allele-specific chromatin binding sequencing (HASCh-seq) approach and identify variations in target binding of the brassinosteroid-responsive TF ZmBZR1 in maize. HASCh-seq in the B73xMo17 F1s identifies thousands of target genes of ZmBZR1. Allele-specific ZmBZR1 binding (ASB) has been observed for 18.3% of target genes and is enriched in promoter and enhancer regions. About a quarter of the ASB sites correlate with sequence variation in BZR1-binding motifs and another quarter correlate with haplotype-specific DNA methylation, suggesting that both genetic and epigenetic variations contribute to the high level of variation in ZmBZR1 occupancy. Comparison with GWAS data shows linkage of hundreds of ASB loci to important yield and disease-related traits.

Conclusion

Our study provides a robust method for analyzing genome-wide variations of TF occupancy and identifies genetic and epigenetic variations of the brassinosteroid response transcription network in maize.
General improvements versus interruptive or non-interruptive alerts in the blood order set: study protocol for a randomized control trial to improve packed red blood cell utilization
Authors: Mistry Neelam , Richardson Vanessa , Carey Evan , Porter Samuel , Pincus Sharon , Novins-Montague Sylvie , Elmer Megan , Lin Chen-Tan , Ho P. Michael , Anstett Tyler
Published: May 2023

Background

Blood transfusions can serve as a life-saving treatment, but inappropriate blood product transfusions can result in patient harm and excess costs for health systems. Despite published evidence supporting restricted packed red blood cell (pRBC) usage, many providers transfuse outside of guidelines. Here, we report a novel prospective, randomized control trial to increase guideline-concordant pRBC transfusions comparing three variations of clinical decision support (CDS) in the electronic health record (EHR).

Methods

All inpatient providers at University of Colorado Hospital (UCH) who order blood transfusions were randomized in a 1:1:1 fashion to the three arms of the study: (1) general order set improvements, (2) general order set improvements plus non-interruptive in-line help text alert, and (3) general order set improvements plus interruptive alert. Transfusing providers received the same randomized order set changes for 18 months. The primary outcome of this study is the guideline-concordant rate of pRBC transfusions. The primary objective of this study is to compare the group using the new interface (arm 1) versus the two groups using the new interface with interruptive or non-interruptive alerts (arms 2 and 3, combined). The secondary objectives compare guideline-concordant transfusion rates between arm 2 and arm 3 as well as comparing all of arms of the study in aggregate to historical controls. This trial concluded after 12 months on April 5, 2022.

Discussion

CDS tools can increase guideline-concordant behavior. This trial will examine three different CDS tools to determine which type is most effective at increasing guideline-concordant blood transfusions.

Trial registration

Registered on ClinicalTrials.gov 3/20/21, NCT04823273. Approved by University of Colorado Institutional Review Board (19–0918), protocol version 1 4/19/2019, approved 4/30/2019.
Imaging features of the PI-RADS for predicting extraprostatic extension of prostate cancer: systematic review and meta-analysis
Authors: Choi Moon Hyung , Kim Dong Hwan , Lee Young Joon , Rha Sung Eun , Lee Ji Youl
Published: May 2023

Objectives

To systematically determine the diagnostic performance of each MRI feature of the PI-RADS for predicting extraprostatic extension (EPE) in prostate cancer.

Methods

A literature search in the MEDLINE and EMBASE databases was conducted to identify original studies reporting the accuracy of each feature on MRI for the dichotomous diagnosis of EPE. The meta-analytic pooled diagnostic odds ratio (DOR), sensitivity, specificity, and their 95% confidence intervals (CIs) were obtained using a bivariate random-effects model.

Results

After screening 1955 studies, 17 studies with a total of 3062 men were included. All six imaging features, i.e., bulging prostatic contour, irregular or spiculated margin, asymmetry or invasion of neurovascular bundle, obliteration of rectoprostatic angle, tumor-capsule interface > 10 mm, and breach of the capsule with evidence of direct tumor extension, were significantly associated with EPE. Breach of the capsule with direct tumor extension demonstrated the highest pooled DOR (15.6, 95% CI [7.7–31.5]) followed by tumor-capsule interface > 10 mm (10.5 [5.4–20.2]), asymmetry or invasion of neurovascular bundle (7.6 [3.8–15.2]), and obliteration of rectoprostatic angle (6.1 [3.8–9.8]). Irregular or spiculated margin showed the lowest pooled DOR (2.3 [1.3–4.2]). Breach of the capsule with direct tumor extension and tumor-capsule interface > 10 mm showed the highest pooled specificity (98.0% [96.2–99.0]) and sensitivity (86.3% [70.0–94.4]), respectively.

Conclusions

Among the six MRI features of prostate cancer, breach of the capsule with direct tumor extension and tumor-capsule interface > 10 mm were the most predictive of EPE with the highest specificity and sensitivity, respectively.

Graphical abstract
An improved integrative GFP-based vector for genetic engineering of Parageobacillus thermoglucosidasius facilitates the identification of a key sporulation regulator
Authors: Millgaard Marie , Bidart Gonzalo Nahuel , Pogrebnyakov Ivan , Nielsen Alex Toftgaard , Welner Ditte Hededam
Published: May 2023

Parageobacillus thermoglucosidasius is a thermophilic Gram-positive bacterium, which is a promising host organism for sustainable bio-based production processes. However, to take full advantage of the potential of P. thermoglucosidasius, more efficient tools for genetic engineering are required. The present study describes an improved shuttle vector, which speeds up recombination-based genomic modification by incorporating a thermostable sfGFP variant into the vector backbone. This additional selection marker allows for easier identification of recombinants, thereby removing the need for several culturing steps. The novel GFP-based shuttle is therefore capable of facilitating faster metabolic engineering of P. thermoglucosidasius through genomic deletion, integration, or exchange. To demonstrate the efficiency of the new system, the GFP-based vector was utilised for deletion of the spo0A gene in P. thermoglucosidasius DSM2542. This gene is known to be a key regulator of sporulation in Bacillus subtilis, and it was therefore hypothesised that the deletion of spo0A in P. thermoglucosiadius would produce an analogous sporulation-inhibited phenotype. Subsequent analyses of cell morphology and culture heat resistance suggests that the P. thermoglucosidasius ∆spo0A strain is sporulation-deficient. This strain may be an excellent starting point for future cell factory engineering of P. thermoglucosidasius, as the formation of endospores is normally not a desired trait in large-scale production.
Infection prevention and control measures for preterm infants discharged into the community: a scoping review protocol
Authors: Carruthers Kathryn , Hannis Dorothy , Robinson Jonathan , Armstrong Alan
Published: May 2023

Background

Infection prevention and control (IPC) is an evidence-based and practical approach to prevention of harm by infection (Infection prevention and control https://www.who.int/health-topics/infection-prevention-and-control#tab=tab_1). IPC recommendations targeted at community-acquired infection aim to prevent illness and subsequent hospital readmission. Cohesive guidance for parents of preterm infants has not been clearly established. The review objectives are to identify and map the global characteristics of IPC measures/recommendations for parents of preterm infants discharged home to the community.

Methods

The scoping review will be conducted using the JBI methodological approach for scoping reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension (PRISMA ScR) and the PRISMA extension for reporting literature searches in systematic reviews. Electronic databases will be searched and limited by publication year (2013-present day). Grey literature, reference lists and expert-provided sources will be searched against predetermined criteria. A minimum of two authors will independently screen evidence sources and chart evidence on a predetermined charting form. Sources including IPC measures, or recommendations for parents of preterm infants during discharge planning or in the community/home, will be permitted within inclusion criteria. Limits include human studies only and evidence from 2013-present day. Recommendations aimed at professional implementation will be excluded. A descriptive summary of findings will be presented, with diagrammatic and tabular representation.

Discussion

Collated evidence will guide future research which will subsequently aim to develop policy and enhance clinical approaches.

Systematic review registration

This review has been registered on the Open Science Framework (OSF) 4th May 2021, available at https://osf.io/9yhzk.
Blockchain-based collaborative edge computing: efficiency, incentive and trust
Authors: Gao Qinghang , Xiao Jianmao , Cao Yuanlong , Deng Shuiguang , Ouyang Chuying , Feng Zhiyong
Published: May 2023

The rise of 5G technology has driven the development of edge computing. Computation offloading is the key and challenging point in edge computing, which investigates offloading resource-intensive computing tasks from the user side to the cloud or edge side for processing. More consideration needs to be given to load balancing, user variability, and the heterogeneity of edge facilities in relevant research. In addition, most of the research around edge collaboration also revolves around cloud-side collaboration, which pays relatively little attention to the collaboration process between edge nodes, and the incentive and trust issues of the collaboration process need to be addressed. In this paper, we consider the impact of the user demand variability and the edge facility heterogeneity, then propose a method based on Vickrey-Clarke-Groves (VCG) auction theory to accommodate the edge demand response (EDR) process where the number of users and service facilities do not match. The method makes users’ bidding rules satisfy the Nash equilibrium and weakly dominant strategy, which can improve the load balancing of edge nodes, has positive significance in improving the edge resource utilization and reducing the system energy consumption. In particular, combined with blockchain, we further optimize the incentive and trust mechanism of edge collaboration and consider three scenarios: no collaboration, internal collaboration, and incentive collaboration. We also consider the impact of the user task’s transmission distance on the quality of experience (QoE). In addition, we illustrate the possible forking attack of blockchain in collaborative edge computing and propose a solution. We test the performance of the proposed algorithm on a real-world dataset, and the experimental results verify the algorithm’s effectiveness and the edge collaboration’s necessity.
Implementation and workflow strategies for integrating digital therapeutics for alcohol use disorders into primary care: a qualitative study
Authors: Mogk Jessica M. , Matson Theresa E. , Caldeiro Ryan M. , Garza Mcwethy Angela M. , Beatty Tara , Sevey Brandie C. , Hsu Clarissa W. , Glass Joseph E.
Published: May 2023

Background

Alcohol use disorders (AUD) are prevalent and often go untreated. Patients are commonly screened for AUD in primary care, but existing treatment programs are failing to meet demand. Digital therapeutics include novel mobile app-based treatment approaches which may be cost-effective treatment options to help fill treatment gaps. The goal of this study was to identify implementation needs and workflow design considerations for integrating digital therapeutics for AUD into primary care.

Methods

We conducted qualitative interviews with clinicians, care delivery leaders, and implementation staff (n = 16) in an integrated healthcare delivery system in the United States. All participants had experience implementing digital therapeutics for depression or substance use disorders in primary care. Interviews were designed to gain insights into adaptations needed to optimize existing clinical processes, workflows, and implementation strategies for use with alcohol-focused digital therapeutics. Interviews were recorded and transcribed and then analyzed using a rapid analysis process and affinity diagramming.

Results

Qualitative themes were well represented across health system staff roles. Participants were enthusiastic about digital therapeutics for AUD, anticipated high patient demand for such a resource, and made suggestions for successful implementation. Key insights regarding the implementation of digital therapeutics for AUD and unhealthy alcohol use from our data include: (1) implementation strategy selection must be driven by digital therapeutic design and target population characteristics, (2) implementation strategies should seek to minimize burden on clinicians given the large numbers of patients with AUD who are likely to be interested in and eligible for digital therapeutics, and (3) digital therapeutics should be offered alongside many other treatment options to accommodate individual patients’ AUD severity and treatment goals. Participants also expressed confidence that previous implementation strategies used with other digital therapeutics such as clinician training, electronic health record supports, health coaching, and practice facilitation would be effective for the implementation of digital therapeutics for AUD.

Conclusions

The implementation of digital therapeutics for AUD would benefit from careful consideration of the target population. Optimal integration requires tailoring workflows to meet anticipated patient volume and designing workflow and implementation strategies to meet the unique needs of patients with varying AUD severity.
Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer
Authors: Alexander James L. , Posma Joram M. , Scott Alasdair , Poynter Liam , Mason Sam E. , Doria M. Luisa , Herendi Lili , Roberts Lauren , McDonald Julie A. K. , Cameron Simon , Hughes David J. , Liska Vaclav , Susova Simona , Soucek Pavel , der Sluis Verena Horneffer-van , Gomez-Romero Maria , Lewis Matthew R. , Hoyles Lesley , Woolston Andrew , Cunningham David , Darzi Ara , Gerlinger Marco , Goldin Robert , Takats Zoltan , Marchesi Julian R. , Teare Julian , Kinross James
Published: May 2023

Background and aims

The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.

Methods

A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.

Results

Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10−11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR = 1.30 × 10−12), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.

Conclusions

Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection.
Highly diverse and unknown viruses may enhance Antarctic endoliths’ adaptability
Authors: Ettinger Cassandra L. , Saunders Morgan , Selbmann Laura , Delgado-Baquerizo Manuel , Donati Claudio , Albanese Davide , Roux Simon , Tringe Susannah , Pennacchio Christa , del Rio Tijana G. , Stajich Jason E. , Coleine Claudia
Published: May 2023

Background

Rock-dwelling microorganisms are key players in ecosystem functioning of Antarctic ice free-areas. Yet, little is known about their diversity and ecology, and further still, viruses in these communities have been largely unexplored despite important roles related to host metabolism and nutrient cycling. To begin to address this, we present a large-scale viral catalog from Antarctic rock microbial communities.

Results

We performed metagenomic analyses on rocks from across Antarctica representing a broad range of environmental and spatial conditions, and which resulted in a predicted viral catalog comprising > 75,000 viral operational taxonomic units (vOTUS). We found largely undescribed, highly diverse and spatially structured virus communities which had predicted auxiliary metabolic genes (AMGs) with functions indicating that they may be potentially influencing bacterial adaptation and biogeochemistry.

Conclusion

This catalog lays the foundation for expanding knowledge of virosphere diversity, function, spatial ecology, and dynamics in extreme environments. This work serves as a step towards exploring adaptability of microbial communities in the face of a changing climate.
Association of virome dynamics with mosquito species and environmental factors
Authors: Liu Qing , Cui Feng , Liu Xiang , Fu Yumei , Fang Wenjing , Kang Xun , Lu Hong , Li Siping , Liu Biao , Guo Wei , Xia Qianfeng , Kang Le , Jiang Feng
Published: May 2023

Background

The pathogenic viruses transmitted by mosquitoes cause a variety of animal and human diseases and public health concerns. Virome surveillance is important for the discovery, and control of mosquito-borne pathogenic viruses, as well as early warning systems. Virome composition in mosquitoes is affected by mosquito species, food source, and geographic region. However, the complex associations of virome composition remain largely unknown.

Results

Here, we profiled the high-depth RNA viromes of 15 species of field-caught adult mosquitoes, especially from Culex, Aedes, Anopheles, and Armigeres in Hainan Island from 2018 to 2020. We detected 57 known and 39 novel viruses belonging to 15 families. We established the associations of the RNA viruses with mosquito species and their foods, indicating the importance of feeding acquisition of RNA viruses in determining virome composition. A large fraction of RNA viruses were persistent in the same mosquito species across the 3 years and different locations, showing the species-specific stability of viromes in Hainan Island. In contrast, the virome compositions of single mosquito species in different geographic regions worldwide are visibly distinct. This is consistent with the differences in food sources of mosquitoes distributed broadly across continents.

Conclusions

Thus, species-specific viromes in a relatively small area are limited by viral interspecific competition and food sources, whereas the viromes of mosquito species in large geographic regions may be governed by ecological interactions between mosquitoes and local environmental factors.
TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma
Authors: Menevse Ayse N. , Ammer Laura-Marie , Vollmann-Zwerenz Arabel , Kupczyk Marcell , Lorenz Julia , Weidner Lorraine , Hussein Abir , Sax Julian , Mühlbauer Jasmin , Heuschneider Nicole , Rohrmus Celine , Mai Laura S. , Jachnik Birgit , Stamova Slava , Volpin Valentina , Durst Franziska C. , Sorrentino Antonio , Xydia Maria , Milenkovic Vladimir M. , Bader Stefanie , Braun Frank K. , Wetzel Christian , Albert Nathalie L. , Tonn Joerg-Christian , Bartenstein Peter , Proescholdt Martin , Schmidt Nils O. , Linker Ralf A. , Riemenschneider Markus J. , Beckhove Philipp , Hau Peter
Published: May 2023

Glioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It is particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) is upregulated in GB and correlates with malignancy and poor prognosis, but also with increased immune infiltration. Here, we studied the role of TSPO in the regulation of immune resistance of human GB cells. The role of TSPO in tumor immune resistance was experimentally determined in primary brain tumor initiating cells (BTICs) and cell lines through genetic manipulation of TSPO expression and subsequent cocultures with antigen specific cytotoxic T cells and autologous tumor-infiltrating T cells. Death inducing intrinsic and extrinsic apoptotic pathways affected by TSPO were investigated. TSPO-regulated genes mediating apoptosis resistance in BTICs were identified through gene expression analysis and subsequent functional analyses. TSPO transcription in primary GB cells correlated with CD8+ T cell infiltration, cytotoxic activity of T cell infiltrate, expression of TNFR and IFNGR and with the activity of their downstream signalling pathways, as well as with the expression of TRAIL receptors. Coculture of BTICs with tumor reactive cytotoxic T cells or with T cell-derived factors induced TSPO up-regulation through T cell derived TNFα and IFNγ. Silencing of TSPO sensitized BTICs against T cell-mediated cytotoxicity. TSPO selectively protected BTICs against TRAIL-induced apoptosis by regulating apoptosis pathways. TSPO also regulated the expression of multiple genes associated with resistance against apoptosis. We conclude that TSPO expression in GB is induced through T cell-derived cytokines TNFα and IFNγ and that TSPO expression protects GB cells against cytotoxic T cell attack through TRAIL. Our data thereby provide an indication that therapeutic targeting of TSPO may be a suitable approach to sensitize GB to immune cell-mediated cytotoxicity by circumventing tumor intrinsic TRAIL resistance.
An impact assessment of the COVID-19 pandemic on Japanese and US hotel stocks
Authors: Kanamura Takashi
Published: May 2023

This study proposes two new regime-switching volatility models to empirically analyze the impact of the COVID-19 pandemic on hotel stock prices in Japan compared with the US, taking into account the role of stock markets. The first model is a direct impact model of COVID-19 on hotel stock prices; the analysis finds that infection speed negatively affects Japanese hotel stock prices and shows that the regime continues to switch to high volatility in prices due to COVID-19 until September 2021, unlike US stock prices. The second model is a hybrid model with COVID-19 and stock market impacts on the hotel stock prices, which can remove the market impacts on regime-switching volatility; this analysis demonstrates that COVID-19 negatively affects hotel stock prices regardless of whether they are in Japan or the US. We also observe a transition to a high-volatility regime in hotel stock prices due to COVID-19 until around summer 2021 in both Japan and the US. These results suggest that COVID-19 is likely to affect hotel stock prices in general, except for the influence of the stock market. Considering the market influence, COVID-19 directly and/or indirectly affects Japanese hotel stocks through the Japanese stock market, and US hotel stocks have limited impacts from COVID-19 owing to the offset between the influence on hotel stocks and no effect on the stock market. Based on the results, investors and portfolio managers should be aware that the impact of COVID-19 on hotel stock returns depends on the balance between the direct and indirect effects, and varies from country to country and region to region.
Understanding who is and isn’t involved and engaged in health research: capturing and analysing demographic data to diversify patient and public involvement and engagement
Authors: Keane Annie , Islam Safina , Parsons Suzanne , Verma Arpana , Farragher Tracey , Forde Davine , Holmes Leah , Cresswell Katharine , Williams Susannah , Arru Paolo , Howlett Emily , Turner-Uaandja Hannah , MacGregor Issy , Grey Tracy , Arain Zahra , Scahill Maura , Starling Bella
Published: May 2023

Background

Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. The aim of this study was to develop to capture and analyse the characteristics of who does and doesn’t take part in patient and public involvement and engagement (PPIE) activities.

Methods

As part of its strategic focus on diversity and inclusion, Vocal developed a questionnaire to assess the demographics of people taking part in its PPIE activities. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. The questionnaire was implemented across Vocal activities between December 2018 and March 2022. In that time. Vocal was working with approximately 935 public contributors. 329 responses were received: a return rate of 29.3%. Analysis of findings and comparison against local population demographic data, and available national data related to public contributors to health research, was performed.

Results

Results show that it is feasible to assess the demographics of people who take part in PPIE activities, through a questionnaire system. Further, our emerging data indicate that Vocal are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in health research, as compared to available national data. Specifically, Vocal involves more people of Asian, African and Caribbean heritage, and includes a wider range of ages in its PPIE activities. More women than men are involved in Vocal’s work.

Conclusion

Our ‘learn by doing’ approach to assessing who does and doesn’t take part in Vocal’s PPIE activities has informed our practice and continues influence our strategic priorities for PPIE. Our system and learning reported here may be applicable and transferable to other similar settings in which PPIE is carried out. We attribute the greater diversity of our public contributors to our strategic priority and activities to promote more inclusive research since 2018.
Structured content and data management—enhancing acceleration in drug development through efficiency in data exchange
Authors: Beierle Jill , Algorri Marquerita , Cortés Marisol , Cauchon Nina S. , Lennard Andrew , Kirwan J. Paul , Oghamian Shirley , Abernathy Michael J.
Published: May 2023

Innovation in pharmaceutical therapeutics is critical for the treatment of serious diseases with unmet medical need. To accelerate the approval of these innovative treatments, regulatory agencies throughout the world are increasingly adopting the use of expedited pathways and collaborative regulatory reviews. These pathways are primarily driven by promising clinical results but become challenging for Chemistry, Manufacturing, and Controls (CMC) information in regulatory submissions. Condensed and shifting timelines present constraints that require new approaches to the management of regulatory filings. This article emphasizes technological advances that have the potential to tackle the underlying inefficiencies in the regulatory filing eco-system.

Structured content and data management (SCDM) is highlighted as a foundation for technologies that can ease the burden on both sponsors and regulators by streamlining data usage in regulatory submissions. Re-mapping of information technology infrastructure will improve the usability of data by moving away from document-based filings towards electronic data libraries. Although the inefficiencies of the current regulatory filing eco-system are more evident for products that are filed using expedited pathways, it is envisioned that the more widespread adoption of SCDM, across standard filing and review processes, will improve overall efficiency and speed in the compilation and review of regulatory submissions.
“I Have Constant Fear”: A National Qualitative Study on the Impact of COVID-19 on Cancer Care and Potential Solutions to Improve the Cancer Care Experience During the COVID-19 Pandemic
Authors: Rodriguez Gladys M. , Kumar Dhanya , Patel Manali I.
Published: May 2023

PURPOSE

The COVID-19 pandemic has greatly affected cancer care delivery for patients, including cancellation or delays in surveillance imaging, clinic visits, and treatments. Yet, gaps remain in understanding the extent of the impact of the COVID-19 pandemic on patients with cancer and potential ways to overcome these impacts.

METHODS

We conducted semistructured, in-depth, one-on-one qualitative interviews among adults with a past or current history of cancer in the United States. Participants from a parent quantitative survey were purposively sampled to participate in a qualitative interview. Interview questions addressed (1) experiences with cancer care delivery during the COVID-19 pandemic; (2) unmet concerns regarding care and other impacts; and (3) approaches to improve patient experiences. We conducted inductive thematic analysis.

RESULTS

Fifty-seven interviews were conducted. Four themes emerged: (1) concern regarding the risk of COVID-19 infection among patients with cancer and their families; (2) disruptions in care increased patients' anxiety about poor cancer outcomes and death from cancer; (3) significant social and economic impacts; and (4) increased social isolation and anxiety about the future. Suggestions for current clinical practice include (1) clear communication on patients' health risks; (2) increased attention to mental health needs and access to mental health services; and (3) routine use of telemedicine as frequently as possible when clinically appropriate.

CONCLUSION

These rich findings reveal the significant impact of the COVID-19 pandemic on patients with cancer and potential approaches to mitigate the impact from the patient perspective. The findings not only inform current cancer care delivery but also health system responses to future public health or environmental crises that may pose a unique health risk for patients with cancer or disrupt their care.
System safety approaches for human-robot collaborative tasks
Authors: Ζαχαράκη Αγγελική
Published: May 2023

Αυτή η διατριβή στοχεύει να παράσχει έναν μηχανισμό λήψης αποφάσεων, όπως ένα εργαλείο σε πραγματικό χρόνο, το οποίο αξιοποιεί τις καθορισμένες μη ασφαλείς ενέργειες ελέγχου που εξάγονται από τη μέθοδο STPA, προκειμένου να ωθήσει το σύστημα στην επιλογή μιας ενέργειας, με βάση τις τρέχουσες και προηγούμενες παρατηρήσεις και ενέργειες, που θα το μεταφέρουν σε μια επόμενη κατάσταση που ανήκει σε υψηλότερο επίπεδο ασφάλειας. Χρησιμοποιούμε μια αφαίρεση για τη ομαδοποίηση της πληθώρας των κανονικών και μη ασφαλών καταστάσεων του συστήματος και διατυπώνουμε το πρόβλημα ως μια μερική παρατηρήσιμη διαδικασία απόφασης Makrov προκειμένου να προσδιορίσουμε ένα γράφημα που λειτουργεί σε πραγματικό χρόνο και συνάγει ασφαλές και το μη ασφαλές ροές εργασιών του συστήματος. Έτσι, η εργασία σε αυτή τη διατριβή δεν παρέχει μόνο ένα θεωρητικό πλαίσιο για αξιόπιστο και ασφαλές HRC σε μη περιορισμένα περιβάλλοντα, αλλά δείχνει επίσης μεγάλες δυνατότητες σε πρακτικές εφαρμογές. Επιπλέον, η προτεινόμενη μέθοδος ασφάλειας παρέχει μια νέα προοπτική για την προβολή και την εφαρμογή ασφαλούς HRC συνδυάζοντας διάφορες μεθοδολογίες σε διαφορετικά ερευνητικά πεδία, συμπεριλαμβανομένης της θεωρίας παρατήρησης, της ομαλότητας των γραφημάτων και των συστημάτων και της θεωρίας ελέγχου.
Gamma spectroscopy of even-even Ytterbium isotopes
Authors: Efstathiou Margarita , Karadimas Angelos , Zyriliou Aikaterini , Vasileiou Polytimos , Mertzimekis Theodoros , Chalil Achment , Pelonis Stefanos
Published: May 2023

The even-even Ytterbium isotopes lack spectroscopic information with the increase of the neutron number and they are well deformed nuclei, presenting rotational properties. In this mass region of the nuclear chart predictions have shown rare phenomena related to nuclear structure, such as shape coexistence. In this work the population of excited states were investigated in the even-even Yb isotopes via the 2n-transfer reaction  168-174Yb (18O, 16O) 170-176Yb. The measurements were carried out at the 9 MV Tandem accelerator at the Horia Hulubei National Institute of Physics and Nuclear Engineering (IFIN-HH) in Romania. The deduced gamma-ray angular distributions in the ground state bands are found to correspond with  transitions, as expected
Recent Progress in the Study of the Reaction 70Zn (15 MeV/nucleon) + 64Ni with the MAGNEX Spectrometer
Authors: Koulouris Stergios , Souliotis Georgios , Cappuzzello Francesco , Carbone Diana , Pakou Athena , Agodi Clementina , Brischetto Giuseppe , Cavallaro Manuela , Calabrese Salvatore , Ciraldo Irene , Fasoula Olga , Klimo Jozef , Palli Konstantina , Sgouros Onoufrios , Soukeras Vasilis , Spatafora Alessandro , Torresi Domenico , Veselsky Martin
Published: May 2023

The present paper is focused on our recent efforts to study the production and identification of neutron-rich medium-mass rare isotopes from peripheral reactions at beam energies around and below the Fermi energy. We obtained high-quality experimental data from a recent experiment with the MAGNEX spectrometer at the INFN-LNS in Catania, Italy. The main aim of this experiment was to check the feasibility of ejectile identification in this energy regime with the use of a large acceptance magnetic spectrometer. Our developed technique for particle identification depends mainly on a reconstruction of both the atomic number Z and the ionic charge q of the ions, followed by the identification of the mass. Our method was successfully applied to identify neutron-rich ejectiles from multinucleon transfer from the reaction of 70Zn (15 MeV/nucleon) + 64Ni. Preliminary results indicate that the extracted experimental distributions, along with comparisons with the theoretical models could help us to shed light to the complex reaction mechanism of multinucleon transfer in this energy regime.
The neutrino floor: a data-driven analysis
Authors: Papoulias Dimitrios K.
Published: May 2023

We reconsider the discovery limit of multi-ton direct detection dark matter experiments in the light of recent measurements of the coherent elastic neutrino-nucleus scattering process. Assuming the cross section to be a parameter entirely determined by data, rather than using its Standard Model prediction, we use the COHERENT CsI and LAr data sets to determine WIMP discovery limits. Being based on a data-driven approach, the results are thus free from theoretical assumptions and fall within the WIMP mass regions where XENONnT and DARWIN have best expected sensitivities. We further determine the impact of subleading nuclear form factor and weak mixing angle uncertainties effects on WIMP discovery limits. We point out that these effects, albeit small, should be taken into account. Moreover, to quantify the impact of new physics effects in the neutrino background, we revisit WIMP discovery limits assuming light vector and scalar mediators as well as neutrino magnetic moments/transitions. We stress that the presence of new interactions in the neutrino sector, in general, tend to worsen the WIMP discovery limit.
Compton Suppression System performance evaluation for measurement of VERDI activation detectors
Authors: Anagnostopoulou Vasiliki , I. Savva Marilia , Vasilopoulou Theodora , Mergia Konstantina , Kokkoris Michael , Stamatelatos Ion E.
Published: May 2023

The VERDI detector was developed for accurate neutron measurements in the plasma-facing modules of a tokamak. It comprises a low activation capsule, capable to withstand the harsh conditions of the fusion environment, containing a defined mass of metallic foils. The neutron fluence and energy spectrum are derived by analysis of the gamma lines produced by neutron activation of the metallic elements. In this work, the use of a Compton Suppression System (CSS) is investigated aiming to enhance the sensitivity of VERDI detector analysis. The CSS consists of a 40% HPGe primary detector coupled to a set of NaI secondary detectors. The apparatus was set to discard signals simultaneously recorded on both primary and secondary detectors, thus lowering the Compton continuum. The VERDI detectors were irradiated at the Joint European Torus (JET) during the 2019 Deuterium-Deuterium (DD) campaign. The CSS performance was studied by calculating peak and continuum suppression factors. The advantage introduced by Compton suppressed gamma spectrometry for each nuclide of interest is explored and the suitability of this system for VERDI detector measurements is discussed.
Measuring radon concentrations in air at the progeny non-secular equilibrium time frame
Authors: Petropoulos Nikolaos , Argyrou Sotia
Published: May 2023

The Nuclear Engineering Laboratory of NTUA (NEL-NTUA) regularly tests radon-in-air concentration measuring instruments. Most common instruments involve open ionization chambers, radon absorbing devices and grab sampling devices. Most types of such instruments do not provide a calibrated radon concentration as soon as the air sampling has ended, since there should exist an adequate time gap, within which sampled radon would reach secular equilibrium with some or most of its immediate progeny. This gap should be around 10-20 min for radon to equilibrate with the Po-218 nucleus, or it could be more than about 3 hours for radon to equilibrate with the Bi-214 / Po-214 progeny. However, if there could be organized calibration experiments at the progeny non-secular equilibrium state, there are some instrument cases, for which this time gap difficulty may be better understood and overcome. To this end, in this work, the Bateman differential equations for all gamma and alpha emitting radon daughters are solved for radon daughters activity at any given time between 0 min and 3 hours using a spreadsheet. This would allow for obtaining a calibration correction factor to be applied at any given time before equilibrium, resulting for radon concentration estimations without the limitations of waiting. Following this solution, the results were theoretically assessed in terms of applicability. Calibration experiments performed for ionization chambers, radon absorbents and Lucas Cells at various radon concentrations in air at the progeny non-secular equilibrium time frame corroborate the theoretical approach.
NORM measurements at Kalloni and Gera Gulfs, Lesvos Island, Greece
Authors: Pappa Filothei
Published: May 2023

Natural radioactivity measurements were held in the beach sands of the two main gulfs (Gera, Kalloni) of Lesvos Island, Greece. These gulfs host thermal springs and are preferred tourist destinations throughout the year. Dose rates and concentrations of natural radioactivity (232Th series, 226Ra and 40K) and 137Cs were measured in-situ and in the laboratory by means of gamma ray spectroscopy. Ten beach sand samples were collected from each gulf. The in-situ measurement and the dose rate determination was achieved via a portable NaI scintillation detector (SpriID). The activity concentration calculations were realized in the laboratory, with the use of a high purity germanium detector, and then they were also used to estimate dose rates. The in-situ measured and estimated dose rates were compared to verify the different approaches. The highest values (activity concentrations and dose rates) were found at the beaches of Kalloni Gulf compared to those of Gera Gulf, which may be attributed to the granulometry.
Prevalence of feeding disorders in healthy infants and children under 3 years of age based on a questionnaire study
Authors: Kamińska-Sobczak Aleksandra , Trafalska Elżbieta , Gaszyńska Ewelina
Published: May 2023

Introduction and purpose

Depending on the source, feeding disorders are common reasons to visit a pediatrician - reported in 2-60% of generally healthy children. This study was designed in order to assess the incidence of feeding difficulties in a group of healthy children aged 6-36 months from the Łódź region and to identify factors that may be related to feeding disorders.

Material and method

The research tool of this study was a questionnaire designed by the authors which consisted of 4 personal data questions, 9 questions about the perinatal and neonatal period, 36 feeding questions, 10 questions about child development and weight gain, 10 questions about previous medical history, 30 questions about symptoms, 8 questions about misbehavior during feeding and 14 sociodemographic questions.

Results

215 parents completed questionnaires. However, 10 of them were rejected because those participants met the exclusion criteria. Finally, 205 children were enrolled in the study. The difficulties in feeding were confirmed by the parents of 66 participants. Children with feeding difficulties were more often attended to specialist ambulatories, had been diagnosed with food allergies, and underwent speech therapy and rehabilitation. Additionally, the analysis showed that feeding disorders in mothers and the occurrence of stressful situations in the family were more frequent in children whose parents reported feeding difficulties.

Conclusions

The incidence of feeding difficulties, in the group of healthy children aged 6-36 months from the Łódź region, was higher than reported in other studies. Therefore there is an urgent need to educate parents on feeding recommendations to modify eating behaviors and overcome feeding disorders, followed by some practical advice on appropriate diet adjustment.
EARLY 20TH-CENTURY AMERICAN TRAVELERS AND ART DEALERS OF THE SPANISH ARTISTIC AND HISTORICAL HERITAGE: ARTHUR AND MILDRED STAPLEY BYNE AND THEIR DOUBLE LIVES AS PLUNDERERS AND TRAVEL WRITERS.
Authors: Ruiz Mas José
Published: May 2023

En este artículo analizo las actividades poco ortodoxas llevadas a cabo por los viajeros y marchantes estadounidenses Arthur Byne y su esposa Mildred Stanley Byne en su búsqueda de tesoros artísticos en España durante el primer tercio del siglo XX. Simultáneamente a su saqueo artístico, los Byne publicaron una serie de valiosas obras sobre arte español, todas ellas profusamente ilustradas con fotografías y mapas. Pongo aquí en contraste su escritura de viajes con su actividad depredadora en España. Los Byne se aprovecharon del atraso y la debilidad política de España, de su corrupción institucional y eclesiástica y de la pobreza del pueblo llano para llevar a cabo sus actividades de saqueo. Su producción literaria entre 1914 y 1924, que comenzó siendo un análisis puramente descriptivo del patrimonio artístico español, fue gradualmente evolucionando hacia el relato de viajes más personal por el país (1925- 26). Sin embargo, tras la estrategia de sus intentos de promover el turismo cultural extranjero en España y de fomentar las visitas in situ de los turistas a los lugares descritos en sus obras, los Byne estaban despojando sigilosamente el tesoro artístico español para venderlo en los EE. UU., práctica que consiguieron disimular durante la redacción de sus narraciones de viajes.
Tree Structure Analysis, Biomass and Carbon Stock of Sal Forests in Central Himalayan Region
Authors: Siddiqui Falak , Lodhiyal L. S.
Published: May 2023

Present study deals with density, species diversity, basal area, IVI, biomass and carbon stock in Sal forests. The study was conducted in three Sal forest sites around Champawat at Tanakpur. Among the fifteen tree species, total density of trees varied between 290-690 ind. ha-1 in all studied forest. The basal area of trees in forests was 50.92 to 78.84 m2 ha-1. Tree species diversity of Sal forests varied from 1.07-2.11. Biomass and carbon stock of trees ranged from 473.3 to 786.8 tha-1 and 224.8- 373.7 tha-1yr-1 respectively. Shorea robusta was dominated species based on density parameter in all studied forest sites. The tree density of Sal forests was slightly on lower side with comparison to natural forests in and around the region. However, density exhibits positive correlation at (p?0.05) with biomass and carbon. But the difference in age and size of Sal trees showed the variation in biomass and carbon stock among the studied forest site. Present study concludes that Sal forests in and around nearby villages were in degraded conditions due to anthropogenic pressure. Thus, the forests must be conserved through judicious management by providing proper scientific inputs for high biomass and carbon.