bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Analytical Validation of a Reverse Transcription Droplet Digital PCR (RT-ddPCR) Assay forPD-L1Transcripts in Circulating Tumor Cells
Authors: Strati Areti , Zavridou Martha , Economopoulou Panagiota , Gkolfinopoulos Stavros , Psyrri Amanda , Lianidou Evi 
Published: December 2020

AbstractBackgroundPD-L1, an immune checkpoint protein, is an important biomarker for monitoring cancer patients during the administration of cancer immunotherapy. Droplet digital PCR (ddPCR), is a highly sensitive and accurate tool for the quantification of cancer biomarkers in liquid biopsy. We report the development and analytical validation of a novel duplex RT-ddPCR assay for the simultaneous quantification of PD-L1 and hypoxanthine phosphoribosyltransferase (HPRT) (used as reference gene) transcripts in circulating tumor cells (CTCs).MethodsRT-ddPCR experimental conditions were first optimized and the assay was analytically validated using synthetic standards and the BB49 and SCC47 cancer cell lines. The developed assay was further applied in 71 peripheral blood (PB) samples from head and neck squamous cell carcinoma (HNSCC) patients and 20 PB samples from healthy donors. PD-L1 and HPRT transcripts were quantified in cDNAs derived from CTCs isolated by a size-dependent microfluidic device. The developed RT-ddPCR assay was directly compared to RT-qPCR using 71 identical patient cDNA samples.ResultsAnalytical sensitivity was 0.64 copies/μL, while estimation of intra- and interassay variation revealed a high reproducibility (within-run CV%:4.7–23%; between-run CV%:13%). Using the developed RT-ddPCR assay 33/71(46.5%) HNSCC patients’ samples were found positive for PD-L1 expression in CTCs, while by using RT-qPCR fewer samples (23/71, 32.4%) were positive (concordance: 55/71, 77.5%).ConclusionsThe developed RT-ddPCR assay for PD-L1 in CTCs is highly sensitive, specific, and reproducible; additionally, it offers improved diagnostic sensitivity over RT-qPCR. The clinical utility of the assay should be prospectively evaluated for the real-time monitoring of CTCs of cancer patients under immunotherapy.
Role Mining Heuristics for Permission-Role-Usage Cardinality Constraints
Authors: Blundo Carlo , Cimato Stelvio , Siniscalchi Luisa 
Published: December 2020

Abstract
Role-based access control (RBAC) has become a de facto standard to control access to restricted resources in complex systems and is widely deployed in many commercially available applications, including operating systems, databases and other softwares. The migration process towards RBAC, starting from the current access configuration, relies on the design of role mining techniques, whose aim is to define suitable roles that implement the given access policies. Some constraints can be used to transform the roles automatically output by the mining procedures and effectively capture the organization’s status under analysis. Such constraints can limit the final configuration characteristics, such as the number of roles assigned to a user, or the number of permissions included in a role, and produce a resulting role set that is effectively usable in real-world situations. In this paper, we consider two constraints: the number of permissions a role can include and the number of roles assigned to any user. In particular, we present two heuristics that produce roles compliant with both constraints and evaluate their performances using both real-world and synthetic datasets.
Pre-pouch Ileitis is Associated with Development of Crohn’s Disease-like Complications and Pouch Failure
Authors: Syal Gaurav , Shemtov Ron , Bonthala Nirupama , Vasiliauskas Eric A , Feldman Edward J , Zaghiyan Karen , Ha Christina Y , McGovern Dermot P B , Targan Stephan R , Melmed Gil Y , Fleshner Phillip R 
Published: December 2020

Abstract

Background and Aims
It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone.

Methods
Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn’s disease [CD]-like complications [non-anastomotic strictures or perianal disease &gt;6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes.

Results
There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p &lt;0.0001]. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications (hazard ratio [HR] 3.8; p = 0.0007), need for surgical/endoscopic interventions [HR 4.1; p = 0.002], and immunosuppressive therapy [HR 5.0; p = 0.0002].

Conclusions
Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.
Differences in baseline characteristics and outcomes of bicuspid and tricuspid aortic valves in surgical aortic valve replacement
Authors: Çelik Mevlüt , Milojevic Milan , Durko Andras P , Oei Frans B.S , Bogers Ad. J.J.C , Mahtab Edris A.F 
Published: December 2020

Abstract

OBJECTIVES
Patients with bicuspid aortic valve (BAV) comprise a substantial portion of patients undergoing surgical aortic valve replacement (SAVR). Our goal was to quantify the prevalence of BAV in the current SAVR ± coronary artery bypass grafting (CABG) population, assess differences in cardiovascular risk profiles and assess differences in long-term survival in patients with BAV compared to patients with tricuspid aortic valve (TAV).

METHODS
Patients who underwent SAVR with or without concomitant CABG and who had a surgical report denoting the relevant valvular anatomy were eligible and included. Prevalence, predictors and outcomes for patients with BAV were analysed and compared to those patients with TAV. Matched patients with BAV and TAV were compared using a propensity score matching strategy and an age matching strategy.

RESULTS
A total of 3723 patients, 3145 of whom (mean age 66.6 ± 11.4 years; 37.4% women) had an operative report describing their aortic valvular morphology, underwent SAVR ± CABG between 1987 and 2016. The overall prevalence of patients with BAV was 19.3% (607). Patients with BAV were younger than patients with TAV (60.6 ± 12.1 vs 68.0 ± 10.7, respectively). In the age-matched cohort, patients with BAV were less likely to have comorbidities, among others diabetes (P = 0.001), hypertension (P &lt; 0.001) and hypercholesterolaemia (P = 0.003), compared to patients with TAV. Twenty-year survival following the index procedure was higher in patients with BAV (14.8%) compared to those with TAV (12.9%) in the age-matched cohort (P = 0.015).

CONCLUSIONS
Substantial differences in the cardiovascular risk profile exist in patients with BAV and TAV. Long-term survival after SAVR in patients with BAV is satisfactory.
Vertical stratification patterns of methanotrophs and their genetic controllers in water columns of oxygen-stratified boreal lakes
Authors: Rissanen Antti J , Saarela Taija , Jäntti Helena , Buck Moritz , Peura Sari , Aalto Sanni L , Ojala Anne , Pumpanen Jukka , Tiirola Marja , Elvert Marcus , Nykänen Hannu 
Published: December 2020

ABSTRACT
The vertical structuring of methanotrophic communities and its genetic controllers remain understudied in the water columns of oxygen-stratified lakes. Therefore, we used 16S rRNA gene sequencing to study the vertical stratification patterns of methanotrophs in two boreal lakes, Lake Kuivajärvi and Lake Lovojärvi. Furthermore, metagenomic analyses were performed to assess the genomic characteristics of methanotrophs in Lovojärvi and the previously studied Lake Alinen Mustajärvi. The methanotroph communities were vertically structured along the oxygen gradient. Alphaproteobacterial methanotrophs preferred oxic water layers, while Methylococcales methanotrophs, consisting of putative novel genera and species, thrived, especially at and below the oxic-anoxic interface and showed distinct depth variation patterns, which were not completely predictable by their taxonomic classification. Instead, genomic differences among Methylococcales methanotrophs explained their variable vertical depth patterns. Genes in clusters of orthologous groups (COG) categories L (replication, recombination and repair) and S (function unknown) were relatively high in metagenome-assembled genomes representing Methylococcales clearly thriving below the oxic-anoxic interface, suggesting genetic adaptations for increased stress tolerance enabling living in the hypoxic/anoxic conditions. By contrast, genes in COG category N (cell motility) were relatively high in metagenome-assembled genomes of Methylococcales thriving at the oxic-anoxic interface, which suggests genetic adaptations for increased motility at the vertically fluctuating oxic-anoxic interface.
Survival of the fittest: how the rice microbial community forces Sarocladium oryzae into pathogenicity
Authors: Peeters K J , Audenaert K , Höfte M 
Published: December 2020

ABSTRACT
The fungus Sarocladium oryzae (Sawada) causes rice sheath rot and produces the phytotoxins cerulenin and helvolic acid. Both toxins show antimicrobial activity but only helvolic acid production in the rice sheath correlates with virulence. Sarocladium oryzae isolates that differ in their toxin production were used to study their interaction with the rice culturable bacterial endophyte community. The diversity and community structure was defined in the edge of sheath rot lesions, followed by a null model-based co-occurrence analysis to discover pairwise interactions. Non-random pairs were co-cultured to study the nature of the interactions and the role of the toxins herein. Compared to healthy sheaths, endophyte diversity strongly increased when infected with the least virulent S. oryzae isolates producing low amounts of toxins. Virulent S. oryzae isolates did not affect diversity but caused strong shifts in species composition. The endophyte community of healthy rice plants was dominated by B. cereus. This bacterium was enriched in lesions produced by low-virulent S. oryzae isolates and caused hyphal lysis. Contrarily, helvolic acid producers eliminated this bacterium from the sheath endosphere. We conclude that S. oryzae needs to produce antibiotics to defend itself against antagonistic rice endophytes to successfully colonize and infect the rice sheath.
The effects of performance-based financing on neonatal health outcomes in Burundi, Lesotho, Senegal, Zambia and Zimbabwe
Authors: Gage Anna , Bauhoff Sebastian 
Published: December 2020

Abstract
Maternal and newborn care has been a primary focus of performance-based financing (PBF) projects, which have been piloted or implemented in 21 countries in sub-Saharan Africa since 2007. Several evaluations of PBF have demonstrated improvements to facility delivery or quality of care. However, no studies have measured the impact of PBF programmes directly on neonatal health outcomes in Africa, nor compared PBF programmes against another. We assess the impact of PBF on early neonatal health outcomes and associated health care utilization and quality in Burundi, Lesotho, Senegal, Zambia and Zimbabwe. We pooled Demographic and Health Surveys and Multiple Indicator Cluster Surveys and apply difference-in-differences analysis to estimate the effect of PBF projects supported by the World Bank on early neonatal mortality and low birthweight. We also assessed the effect of PBF on intermediate outputs that are frequently explicitly incentivized in PBF projects, including facility delivery and antenatal care utilization and quality, and caesarean section. Finally, we examined the impact among births to poor or high-risk women. We found no statistically significant impact of PBF on neonatal health outcomes, health care utilization or quality in a pooled sample. PBF was also not associated with better health outcomes in each country individually, though in some countries and among poor women PBF improved facility delivery, antenatal care utilization or antenatal care quality. There was no improvement on the health outcomes among poor or high-risk women in the five countries. PBF had no impact on early neonatal health outcomes in the five African countries studied and had limited and variable effects on the utilization and quality of neonatal health care. These findings suggest that there is a need for both a deeper assessment of PBF and for other strategies to make meaningful improvements to neonatal health outcomes.
Baranov's contributions to the Beverton–Holt model
Authors: Kenchington Trevor J 
Published: December 2020

Abstract
The core of Beverton and Holt’s seminal work of the 1950s had been anticipated by Baranov 30 years earlier, but his contributions, published in Russian, remained poorly known to Anglophone scientists until after 1945. By that time, Russell and Graham had presented parallel ideas, though without Baranov’s mathematics. Limited subsequent acknowledgement of the Russian’s contributions has left an impression that each of his advances was achieved independently in England, hence that they contributed little to the Beverton–Holt model. I here construct a timeline of events linking and separating the Russian and English studies. From it, I argue that both Russell’s presentation of the underlying concepts and Graham’s decision to pursue a mathematical realization of his “Modern Theory” may have been influenced by translations of Baranov’s papers. Moreover, when Holt developed the “simple” Beverton–Holt model during 1946–1947, he certainly drew on Baranov’s exponential model of mortality, though perhaps only via Ricker.
Using Wood’s glass to enhance the efficiency of a water solar disinfection (SODIS) apparatus with a Fresnel lens
Authors: Alkhalidi Ammar , Arabasi Sameer , Othman Abeer Abu , Sabanikh Tareq , Mahmood Linda , Abdelal Qasem 
Published: December 2020

Abstract
Solar disinfection, as a low carbon technology, is a sustainable and cost-effective water treatment method, which makes it more likely to be implemented in developing countries. It has been proven that ultraviolet light radiation is effective against pathogens and microorganisms. The aim of this paper is to evaluate the performance of solar disinfection apparatus that is equipped with Wood’s glass and a Fresnel lens. Wood’s glass is a band-pass filter that allows ultraviolet light to go through and blocks most of the remaining spectrum including infrared. This serves a dual purpose. It lets through the part that inactivates pathogens and microorganisms (ultraviolet) and blocks the part that helps the growth of bacteria (infrared). Experimental setup is designed to investigate the effect of Wood’s glass with and without a Fresnel lens on the solar disinfection process. The investigation is done on a batch-based system and on a novel instantaneous water disinfection system. Results of water disinfection process were recorded for each set of experiments taking into considerations vital parameters, such as solar radiation, solar ultraviolet light intensity and water temperature. The results of these experiments showed effective water disinfection up to 85% pathogens removal by the use of daily available solar radiation.
On the Exceptional Sets of Integral Quadratic Forms
Authors: Chan Wai Kiu , Oh Byeong-Kweon 
Published: December 2020

Abstract
A collection $\mathcal S$ of equivalence classes of positive definite integral quadratic forms in $n$ variables is called an $n$-exceptional set if there exists a positive definite integral quadratic form, which represents all equivalence classes of positive definite integral quadratic forms in $n$ variables except those in $\mathcal S$. We show that, among other results, for any given positive integers $m$ and $n$, there is always an $n$-exceptional set of size $m$ and there are only finitely many of them.
Electronic consultations and clinician burnout: An antidote to our emotional pandemic?
Authors: Lee Michelle S , Nambudiri Vinod E 
Published: December 2020

Abstract
Health information technology is a major source of clinician burnout due to increased administrative burden and inefficient work processes. Electronic consultations (eConsults) represent a promising innovation to improve access to specialty care by reducing wait times for specialist visits and reducing unnecessary in-person specialist visits. While eConsults have clear benefits for patients and healthcare systems, their potential effects on provider burnout should be considered. Using a framework which outlines that the loss of autonomy, competence, and relatedness as the main contributing factors to clinician “amotivation” and burnout, we discuss the use of eConsults and their potential to mitigate or exacerbate burnout for primary care providers and specialists, as well as recommendations for implementation of eConsults to reduce burnout.
A sweet protein monellin as a non-antibody scaffold for synthetic binding proteins
Authors: Yasui Norihisa , Nakamura Kazuaki , Yamashita Atsuko 
Published: December 2020

AbstractSynthetic binding proteins that have the ability to bind with molecules can be generated using various protein domains as non-antibody scaffolds. These designer proteins have been used widely in research studies, as their properties overcome the disadvantages of using antibodies. Here, we describe the first application of a phage display to generate synthetic binding proteins using a sweet protein, monellin, as a non-antibody scaffold. Single-chain monellin (scMonellin), in which two polypeptide chains of natural monellin are connected by a short linker, has two loops on one side of the molecule. We constructed phage display libraries of scMonellin, in which the amino acid sequence of the two loops is diversified. To validate the performance of these libraries, we sorted them against the folding mutant of the green fluorescent protein variant (GFPuv) and yeast small ubiquitin-related modifier. We successfully obtained scMonellin variants exhibiting moderate but significant affinities for these target proteins. Crystal structures of one of the GFPuv-binding variants in complex with GFPuv revealed that the two diversified loops were involved in target recognition. scMonellin, therefore, represents a promising non-antibody scaffold in the design and generation of synthetic binding proteins. We termed the scMonellin-derived synthetic binding proteins ‘SWEEPins’.
Homo religiosus: The Soul of Bioethics
Authors: Stempsey William E 
Published: December 2020

AbstractAlthough many of the pioneers of present-day bioethics came from religious and theological backgrounds, the recent controversy about the role of religion in bioethics has elicited much attention. Timothy Murphy would ban religion from bioethics altogether. Much of the ado hinges on conflicting understandings of just what bioethics is and just what religion is. This paper attempts to make more explicit how the fields of bioethics and religion have been understood in this context, and how they should not be understood. We begin by looking at bioethics as a field: its origins, purpose, scope, and its methods. We then examine the notion of religion, looking especially at its importance for bioethics. Humanity is not just Homo sapiens but also Homo religiosus. Religion is more than a code of ethics; it gives insight into many of the foundational matters of bioethics.
Racial Disparities in Epigenetic Aging of the Right vs Left Colon
Authors: Devall Matthew , Sun Xiangqing , Yuan Fangcheng , Cooper Gregory S , Willis Joseph , Weisenberger Daniel J , Casey Graham , Li Li 
Published: December 2020

Abstract
There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.
Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients
Authors: Yasuda Koichi , Minatogawa Hideki , Dekura Yasuhiro , Takao Seishin , Tamura Masaya , Tsushima Nayuta , Suzuki Takayoshi , Kano Satoshi , Mizumachi Takatsugu , Mori Takashi , Nishioka Kentaro , Shido Motoyasu , Katoh Norio , Taguchi Hiroshi , Fujima Noriyuki , Onimaru Rikiya , Yokota Isao , Kobashi Keiji , Shimizu Shinichi , Homma Akihiro , Shirato Hiroki , Aoyama Hidefumi 
Published: December 2020

Abstract
Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P &lt; 0.05), 46.7 and 76.3% for dysgeusia (P &lt; 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P &lt; 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.