bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational model for detector timing effects in Compton-camera based prompt-gamma imaging for proton radiotherapy
Authors: Maggi Paul , Peterson Steve , Panthi Rajesh , Mackin Dennis , Yang Hao , He Zhong , Beddar Sam , Polf Jerimy 
Published: April 2020

Abstract
This paper describes a realistic simulation of a Compton-camera (CC) based prompt-gamma (PG) imaging system for proton range verification for a range of clinical dose rates, and its comparison to PG measured data with a pre-clinical CC. We used a Monte Carlo plus Detector Effects (MCDE) model to simulate the production of prompt gamma-rays (PG) and their energy depositions in the CC. With Monte Carlo, we simulated PG emission resulting from irradiation of a high density polyethylene phantom with a 150 MeV proton pencil beam at dose rates of 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s−1. Realistic detector timing effects (e.g. delayed triggering time, event-coincidence, dead time, etc,) were added in post-processing to allow for flexible count rate variations. We acquired PG emission measurements with our pre-clinical CC during irradiation with a clinical 150 MeV proton pencil beam at the same dose rates. For simulations and measurements, three primary changes could be seen in the PG emission data as the dose rate increased: (1) reduction in the total number of detected events due to increased dead-time percentage; (2) increase in false-coincidence events (i.e. multiple PGs interacting, rather than a single PG scatter); and (3) loss of distinct PG emission peaks in the energy spectrum. We used the MCDE model to estimate the quality of our measured PG data, primarily with regards to true and false double-scatters and triple-scatters recorded by the CC. The simulation results showed that of the recorded double-scatter PG interactions 22%, 57%, and 70% were false double-scatters and for triple-scatter interactions 3%, 21%, and 35% were false events at 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s−1, respectively. These false scatter events represent noise in the data, and the high percentage of these events in the data represents a major limitation in our ability to produce usable PG images with our prototype CC.
Scoring of Programmed Death-Ligand 1 Immunohistochemistry on Cytology Cell Block Specimens in Non–Small Cell Lung Carcinoma
Authors: Hernandez Andrea , Brandler Tamar C , Chen Fei , Zhou Fang , Xia Yuhe , Zhong Judy , Moreira Andre L , Simms Anthony , Sun Wei , Wei Xiao Jun , Simsir Aylin 
Published: April 2020

Abstract

Objectives
Recent investigations have shown strong correlations between cytology and surgical non–small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement.

Methods
PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (&lt;1%), low positive (1%-49%), and high positive (≥50%) and interrater agreement were assessed.

Results
Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with κ = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (κ = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (κ = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters.

Conclusions
There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.
A Snapshot of Doctoral Training in Epidemiology: Positioning Us for the Future
Authors: Hlaing WayWay M , Schmidt Renae D , Ahn Soyeon , Samet Jonathan M , Brownson Ross C 
Published: April 2020

Abstract
Although epidemiology core competencies are established by the Association of Schools and Programs of Public Health for masters-level trainees, no equivalent currently exists for the doctoral level. Thus, the objective of the Doctoral Education in Epidemiology Survey (2019) was to collect information on doctoral-level competencies in general epidemiology (doctoral) degree programs and other pertinent information from accredited programs in the United States and Canada. Participants (doctoral program directors or knowledgeable representatives of the program) from 57 institutions were invited to respond to a 39-item survey (18 core competencies; 9 noncore or emerging topic–related competencies; and 12 program-related items). Participants from 55 institutions (96.5%) responded to the survey, of whom over 85% rated 11 out of 18 core competencies as “very important” or “extremely important.” More than 80% of the programs currently emphasize 2 of 9 noncore competencies (i.e., competency to ( 1) develop and write grant proposals, and ( 2) assess evidence for causality on the basis of different causal inference concepts). “Big data” is the most frequently cited topic currently lacking in doctoral curricula. Information gleaned from previous efforts and this survey should prompt a dialog among relevant stakeholders to establish a cohesive set of core competencies for doctoral training in epidemiology.
A compounding compliance team at an academic medical center
Authors: Chaffee Bruce W , Tharp Jamie C , Clark John S , Kent Stanley 
Published: April 2020

Abstract

Purpose
Highly publicized safety issues arising from poor sterile compounding practices in facilities around the United States have garnered substantial attention in recent years. This attention has led to increased scrutiny of health systems by regulatory bodies, new regulatory requirements, and changes to existing regulations or their interpretation. Health systems are often resource constrained, and the added work resulting from this scrutiny challenges pharmacy departments in meeting regulatory requirements and United States Pharmacopeia chapter 797 standards for sterile compounding. This article describes the creation of a dedicated compounding compliance team (CCT) and the team’s responsibilities in support of pharmacy operations in achieving compliance with those standards.

Summary
Visits to our organization by several regulatory bodies resulted in findings that required substantial work in order to achieve compliance with sterile compounding standards. Given the number and complexity of findings and the need for timely resolution, it was felt that specialized staff were needed to understand, evaluate, and correct identified deficiencies and help the already overburdened staff and leadership comply with existing standards. A CCT was formed, and work was simultaneously initiated on ensuring proper credentialing and training of all compounding staff, development of standard operating procedures, improvements in facilities, environmental monitoring, equipment certifications, practice auditing, and documentation. Key activities of the team included strategic planning, building relationships, communicating with stakeholders, self-education, and record keeping. Key partners included environmental services, facilities, and infection prevention and control personnel and departmental staff and leaders.

Conclusion
The formation and collaborative work of a CCT at an academic medical center was successful in changing the culture of the organization and achieving compliance during visits from several regulatory agencies.
Isolation gowns as a potential work hazard
Authors: Schirmer Abigail , Sessions Renard , Gravenstein Nikolaus , Rand Kenneth , Oli Monika , Cooper Lou Ann , Sappenfield Joshua W 
Published: April 2020

Abstract

Objectives
Isolation gowns are used as a barrier to bacterial transmission from patient to provider and vice versa. If an isolation gown is ineffective, the patient and provider have a potential breach of safety and increased infection risk. This study compared the bacterial permeability of differently rated, commonly uses isolation gowns to assess their effectiveness in preventing simulated bacterial transmittance, and thus contamination, from patient to provider.

Methods
Serial dilutions of Staphylococcus epidermidis in sterile saline were applied to a simulated skin surface. Unrated and Levels 1 through 4 non-sterile isolation gowns contacted the solution, simulating patient contact. Both sides of the contaminated gowns were then cultured on blood agar by rolling a sterile swab across the gown and evenly inoculating the culture plate. Colony counts from inside and outside of the gowns were compared. Separately, S. epidermidis was placed on a sample of each gown and scanning electron microscopy was used to visualize the contaminated gowns’ physical structure.

Results
Mean bacterial transmittance from outside of the gown (i.e. patient contact side) to inside of the gowns (i.e. provider clothing or skin side) based on gown rating was as follows: unrated: 50.4% (SD 9.0%); Level 1: 39.7% (SD 11.2%); Level 2: 16.3% (SD 10.3%); Level 3: 0.3% (SD 0.8%); Level 4: 0.0% (SD 0.0%). Scanning electron microscope imaging of unrated, Level 1, and Level 2 gowns revealed gown pore sizes much larger than the bacteria. The Welch one-way analysis of variance statistic showed significant difference dependent on gown-level rating.

Conclusions
Unrated, Level 1, and Level 2 isolation gowns do not provide effective bacterial isolation barriers when bacteria like S. epidermidis make contact with one side of the gown material. Not studied, but implied, is that unrated and lower rated isolation gowns would be as or even more physically permeable to virus particles, which are much smaller than bacteria.
How plant allometry influences bud phenology and fruit yield in two Vaccinium species
Authors: Fournier Marie-Pier , Paré Maxime C , Buttò Valentina , Delagrange Sylvain , Lafond Jean , Deslauriers Annie 
Published: April 2020

AbstractBackground and AimsUnderstanding how plant allometry, plant architecture and phenology contribute to fruit production can identify those plant traits that maximize fruit yield. In this study, we compared these variables and fruit yield for two shrub species, Vaccinium angustifolium and Vaccinium myrtilloides, to test the hypothesis that phenology is linked to the plants’ allometric traits, which are predictors of fruit production.MethodsWe measured leaf and flower phenology and the above-ground biomass of both Vaccinium species in a commercial wild lowbush blueberry field (Quebec, Canada) over a 2-year crop cycle; 1 year of pruning followed by 1 year of harvest. Leaf and flower phenology were measured, and the allometric traits of shoots and buds were monitored over the crop cycle. We hand-collected the fruits of each plant to determine fruit attributes and biomass.Key ResultsDuring the harvesting year, the leafing and flowering of V. angustifolium occurred earlier than that of V. myrtilloides. This difference was related to the allometric characteristics of the buds due to differences in carbon partitioning by the plants during the pruning year. Through structural equation modelling, we identified that the earlier leafing in V. angustifolium was related to a lower leaf bud number, while earlier flowering was linked to a lower number of flowers per bud. Despite differences in reproductive allometric traits, vegetative biomass still determined reproductive biomass in a log–log scale model.ConclusionsGrowing buds are competing sinks for non-structural carbohydrates. Their differences in both number and characteristics (e.g. number of flowers per bud) influence levels of fruit production and explain some of the phenological differences observed between the two Vaccinium species. For similar above-ground biomass, both Vaccinium species had similar reproductive outputs in terms of fruit biomass, despite differences in reproductive traits such as fruit size and number.
Targeted histone demethylation improves somatic cell reprogramming into cloned blastocysts but not postimplantation bovine concepti†
Authors: Meng Fanli , Stamms Kathrin , Bennewitz Romina , Green Andria , Oback Fleur , Turner Pavla , Wei Jingwei , Oback Björn 
Published: April 2020

Abstract
Correct reprogramming of epigenetic marks in the donor nucleus is a prerequisite for successful cloning by somatic cell transfer (SCT). In several mammalian species, repressive histone (H) lysine (K) trimethylation (me3) marks, in particular H3K9me3, form a major barrier to somatic cell reprogramming into pluripotency and totipotency. We engineered bovine embryonic fibroblasts (BEFs) for the doxycycline-inducible expression of a biologically active, truncated form of murine Kdm4b, a demethylase that removes H3K9me3 and H3K36me3 marks. Upon inducing Kdm4b, H3K9me3 and H3K36me3 levels were reduced about 3-fold and 5-fold, respectively, compared with noninduced controls. Donor cell quiescence has been previously associated with reduced somatic trimethylation levels and increased cloning efficiency in cattle. Simultaneously inducing Kdm4b expression (via doxycycline) and quiescence (via serum starvation) further reduced global H3K9me3 and H3K36me3 levels by a total of 18-fold and 35-fold, respectively, compared with noninduced, nonstarved control fibroblasts. Following SCT, Kdm4b-BEFs reprogrammed significantly better into cloned blastocysts than noninduced donor cells. However, detrimethylated donors and sustained Kdm4b-induction during embryo culture did not increase the rates of postblastocyst development from implantation to survival into adulthood. In summary, overexpressing Kdm4b in donor cells only improved their reprogramming into early preimplantation stages, highlighting the need for alternative experimental approaches to reliably improve somatic cloning efficiency in cattle.
Distinct follicular and luteal transcriptional profiles in engineered human ectocervical tissue dependent on menstrual cycle phase
Authors: McKinnon Kelly E , Getsios Spiro , Woodruff Teresa K 
Published: April 2020

Abstract
To investigate genomic pathways that may influence physiology and infectivity during the menstrual cycle, RNA sequence analysis was performed on patient-matched engineered ectocervical tissue after follicular and luteal phase (LP) hormone treatments. We developed distinct cellular, molecular, and biological profiles in ectocervical epithelium dependent on the menstrual cycle phase. Follicular phase hormones were associated with proliferation, transcription, and cell adhesion, while LP samples expressed genes involved in immune cell recruitment, inflammation, and protein modifications. Additionally, our analysis revealed mucins not previously reported in ectocervical tissue, which could play an important role in fertility and disease prevention. This study provides insight into the phenomenon of increased LP vulnerability to infection and identifies potential targets for future research.
NRF2 as a regulator of cell metabolism and inflammation in cancer
Authors: He Feng , Antonucci Laura , Karin Michael 
Published: April 2020

AbstractNuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor-promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer-supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation.
The syndrome of inappropriate antidiuresis in COVID-19 pneumonia: report of two cases
Authors: Ravioli Svenja , Niebuhr Norbert , Ruchti Chantal , Pluess Emanuel , Stoeckli Thomas , Lindner Gregor 
Published: April 2020

Abstract
The emergence of the novel coronavirus or severe acute respiratory syndrome coronavirus 2 leads to a high number of cases of severe pneumonia. So far, little is known about the course of the disease and its symptoms, complications and treatment. We report the first two cases of the syndrome of inappropriate antidiuresis complicating COVID-19 pneumonia.
About Physiocracy: A Review Article Incorporating Some Remarks on An Important Letter of Galiani and on The Dissemination and Readership of Quesnay’s Works*
Authors: Sabbagh Gabriel 
Published: April 2020

Abstract
This paper is a review of a substantial collection of essays dealing with Physiocracy and its opponents. Its review led to the first correct reading of an important letter of Galiani and to some new clarifications on the readership of the works of François Quesnay.
JEL Classification: B11; B31.
Monitoring Inflammatory Bowel Disease in Pregnancy Using Gastrointestinal Ultrasonography
Authors: Flanagan Emma , Wright Emily K , Begun Jakob , Bryant Robert V , An Yoon-Kyo , Ross Alyson L , Kiburg Katerina V , Bell Sally J 
Published: April 2020

Abstract

Background and Aims
Inflammatory bowel disease [IBD] affects women during their childbearing years. Gastrointestinal ultrasonography [GIUS] accurately identifies disease activity in non-pregnant patients with IBD. The utility of GIUS in pregnancy has not been established. We aimed to determine the feasibility and accuracy of GIUS in the assessment of IBD during pregnancy progression.

Methods
A multicentre observational study of women with IBD undergoing GIUS during pregnancy. Clinicians assessed the adequacy of bowel views and disease activity in four colonic segments and the terminal ileum. Location[s] in which views were impeded by the uterus were documented. GIUS disease activity [bowel wall thickness &gt;3 mm] was compared with biochemical disease activity [faecal calprotectin &gt;100 μg/g].

Results
Ninety patients and 127 GIUS examinations were included [median gestation 19 weeks, range 4–33]. Adequate colonic views were obtained in 116/127 [91%] scans. Adequate ileal views were obtained in 62/67 [93%] scans &lt;20 weeks and 30/51 [59%] scans at 20–26 weeks. There was a positive correlation between bowel wall thickness and calprotectin [r = 0.26, p = 0.03]. GIUS delivered a specificity of 83%, sensitivity of 74%, and negative predictive value of 90% compared with calprotectin.

Conclusions
GIUS is a feasible and accurate modality for monitoring IBD in pregnancy. Adequate GIUS views of the colon and terminal ileum can be obtained in the majority of patients up to 20 weeks of gestation. Beyond 20 weeks, GIUS provides good views of the colon but the terminal ileum becomes difficult to assess.
Novel synthetic lipopeptides derived from Mycoplasma hyorhinis upregulate calpastatin in SH-SY5Y neuroblastoma cells and induce a neuroprotective effect against amyloid-β-peptide toxicity
Authors: Kornspan Jonathan D , Kosower Nechama S , Vaisid Tali , Katzhandler Joshua , Rottem Shlomo 
Published: April 2020

ABSTRACT
Previously, we showed that contamination of SH-SY5Y neuroblastoma cells by Mycoplasma hyorhinis strains NDMh and MCLD leads to increased levels of calpastatin (the endogenous, specific inhibitor of the Ca2+-dependent protease calpain), resulting in inhibition of calpain activation. We have found that the increased calpastatin level is promoted by the lipoprotein fraction (MhLpp) of the mycoplasmal membrane. Here, we present MhLpp-based novel synthetic lipopeptides that induce upregulation of calpastatin in SH-SY5Y neuroblastoma cells, leading to protection of the treated cells against Ca2+/amyloid-β-peptide toxicity. These lipopeptides present a new class of promising agents against calpain-induced cell toxicity.
Trade Plants the Flag: Sanctions-busting and the Signing of New Preferential Trade Agreements
Authors: Su Yi-hao 
Published: April 2020

Abstract
Why does the imposition of trade sanctions sometimes lead to the signing of new preferential trade agreements (PTAs) between target countries and their trade partners? I argue that the occurrence of trade-based sanctions-busting behavior increases the likelihood of signing new PTAs despite the pressure from senders of sanctions. The notion that “trade plants the flag” explains how firms that bust sanctions lobby their home governments for signing PTAs to secure their first-mover advantage in a sanctioned market. By using rare event models and weighting methods, this empirical analysis of data from 1950 to 2006 reveals that firms’ rent-seeking behavior is the driving force of seeking PTAs especially during multilateral trade sanctions. Thus, this finding can illuminate sanctions agenda as firm-level transactions may serve as a determinant of state-led institutionalized cooperation after the execution of sanctions.
Source-independent efficient wavefield inversion
Authors: Song Chao , Alkhalifah Tariq 
Published: April 2020

SUMMARYFull-waveform inversion (FWI) is an effective tool to retrieve a high-resolution subsurface velocity model. The source wavelet accuracy plays an important role in reaching that goal. So we often need to estimate the source function before or within the inversion process. Source estimation requires additional computational cost, and an inaccurate source estimation can hamper the convergence of FWI. We develop a source-independent waveform inversion utilizing a recently introduced wavefield reconstruction based method, which we refer to as efficient wavefield inversion (EWI). In EWI, we essentially reconstruct the wavefield by fitting it to the observed data as well as a wave equation based on iterative Born scattering. However, a wrong source wavelet will induce errors in the reconstructed wavefield, which may lead to a divergence of this optimization problem. We use a convolution-based source-independent misfit function to replace the conventional data fitting term in EWI to formulate a source-independent EWI (SIEWI) objective function. By convolving the observed data with a reference trace from the predicted data and convolving the predicted data with a reference trace from the observed data, the influence of the source wavelet on the optimization is mitigated. In SIEWI, this new formulation is able to mitigate the cycle-skipping issue and the source wavelet uncertainty simultaneously. We demonstrate those features on the Overthrust model and a modified Marmousi model. Application on a 2-D real data set also shows the effectiveness of the proposed method.
Deportment, emotion and moderation at the Glasgow Assembly, 1638
Authors: Langley Chris R 
Published: April 2020

Abstract
This article explores emotion and behaviour at the Glasgow Assembly in 1638. Whereas the assembly is usually viewed as a masterclass of gerrymandering and control, this article investigates the ways in which participants at the assembly understood the importance of how they behaved, as well as what they said. While both Covenanters and supporters of the Crown were eager to emphasize the ways they moderated their behaviour, they also perpetrated intense bouts of emotional drama. The unrestrained nature of these outbursts underlines the complex relationship between utterance, behaviour and emotion in early modern Calvinism, and in Covenanted Scotland in particular.