bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Alterations in Patients With IBD-associated Colorectal Cancer
Authors: Biscaglia Giuseppe , Latiano Anna , Castellana Stefano , Fontana Rosanna , Gentile Annamaria , Latiano Tiziana , Corritore Giuseppe , Panza Anna , Nardella Marianna , Martino Giuseppina , Bossa Fabrizio , Perri Francesco , Mazza Tommaso , Andriulli Angelo , Palmieri Orazio 
Published: August 2021

Abstract

Background
Patients with inflammatory bowel diseases (IBD), both ulcerative colitis (UC) and Crohn’s disease (CD), are at risk of developing a colorectal cancer (CRC). No information is available on the contribution of patients’ genetic background to CRC occurrence. This study investigates germline alterations in patients with IBD-associated CRC.

Methods
We profiled a panel of 39 genes potentially involved in cancer predisposition and searched for germline variants in IBD patients with CRC or high-grade dysplasia.

Results
After clinical exclusion of genetic cancer syndromes, 25 IBD patients (4 CD and 21 UC) with CRC or high-grade dysplasia were studied. After excluding variants with low likelihood of pathogenicity (classes 1 or 2 according the International Agency for Research on Cancer [IARC]), the panel identified pathogenic variants, likely pathogenic, or variants with unknown significance in 18 patients (72%). Six patients (24%) carried pathogenic or likely variants (IARC class 5 or 4). Of the identified variants, 4 encompassed the APC region, 3 the MLH1 gene, and the remaining ones the MSH2, MSH3, monoallelic MUTYH, EPCAM, BRCA1, CHEK2, POLD1, POLE, CDKN2A, and PDGFRA genes. Four patients carried at least 2 variants in different genes. Duration of IBD was significantly shorter in carriers of 4 or 5 IARC variants (7 years; range 0–21; P = .002) and in those with variants with unknown significance (12 years; range 0–22; P = .005) compared with patients without or with only benign variations (23.5 years; range 15–34).

Conclusions
In silico analysis and sequence-based testing of germline DNA from IBD patients with CRC or high-grade dysplasia detected 24% of variants positioned in pathogenic classes. In patients with type 3, 4, and 5 variants, the onset of high-grade dysplasia or CRC was significantly earlier than in patients with benign or unidentified variants. The screening for these genes could identify IBD patients requiring a more intensive endoscopic surveillance for earlier detection of dysplastic changes.
A Novel Gaze Input System Based on Iris Tracking With Webcam Mounted Eyeglasses
Authors: Yildiz Metin , Yorulmaz Muhammet 
Published: August 2021

AbstractDue to the high cost of eye-tracking systems based on pupillary corneal reflections, efforts to develop a webcam-based eye-tracking system have increased to provide an affordable alternative to disabled people in recent years. However, due to the camera specification and location, ambient light changes and positional changes of the users, the gazing point of the eyes has not yet been determined precisely by such a system. Therefore, only 8 different gaze directions or up to 10 gaze regions could be detected in the previous webcam-based human–computer interaction studies. In this study, a novel gaze input system has been proposed to make the best use of the limited performance of webcam-based eye tracking and offer an economical alternative for disabled people. To reduce the impact of head movements, the webcam has been mounted to an ordinary glasses frame and positioned in front of the eye. For estimation of the gaze regions, a feature-based method (Hough transformation) was used by considering the circular shape of the iris and the contrast between the iris and sclera. The central coordinates of the iris image captured by the webcam were given to the k-nearest neighbor classifier. We performed a series of experiments with 20 subjects to determine the performance of the system and to investigate the effect of ambient light on the system’s accuracy. The 23 regions that were gazed at by subjects were determined with an average accuracy of 99.54%. When the ambient light level was reduced by half, the accuracy decreased to 94.74%. As a result, it has been found that the proposed prototype allows more accurate recognition of a larger number of regions on the screen than previous webcam-based systems. It has been observed that system performance decreases if the ambient light is reduced byhalf.
Antisense inhibition of the Escherichia coli NrdAB aerobic ribonucleotide reductase is bactericidal due to induction of DNA strand breaks
Authors: Campion Christopher , Charbon Godefroid , Thomsen Thomas T , Nielsen Peter E , Løbner-Olesen Anders 
Published: August 2021

Abstract

Background
Antisense peptide nucleic acids (PNAs) constitute an alternative to traditional antibiotics, by their ability to silence essential genes.

Objectives
To evaluate the antibacterial effects of antisense PNA-peptide conjugates that target the gene encoding the alpha subunit (NrdA) of the Escherichia coli ribonucleotide reductase (RNR).

Methods
Bacterial susceptibility of a series of NrdA-targeting PNAs was studied by MIC determination and time–kill analysis. Western-blot analysis, gene complementation and synergy with hydroxyurea were employed to determine the efficiency of NrdA-PNA antisense treatment. The effect on chromosome replication was addressed by determining the DNA synthesis rate, by flow cytometry analysis, by quantitative PCR and by fluorescence microscopy. The use of DNA repair mutants provided insight into the bactericidal action of NrdA-PNA.

Results
Treatment with NrdA-PNA specifically inhibited growth of E. coli, as well as NrdA protein translation at 4 μM. Also, the DNA synthesis rate was reduced, preventing completion of chromosome replication and resulting in formation of double-stranded DNA breaks and cell death.

Conclusions
These data present subunits of the NrdAB RNR as a target for future antisense microbial agents and provide insight into the bacterial physiological response to RNR-targeting antimicrobials.
Debt, Growth and Stability in Africa: Speculative Calculations and Policy Responses
Authors: Devarajan Shantayanan , Gill Indermit S , Karakülah Kenan 
Published: August 2021

Abstract
Since 2014, almost all African countries have experienced an increase in public debt and a change in its nature. The ratio of public debt to GDP has doubled, and sovereign debt is changing from concessional credit provided by official agencies to market-based loans from private institutions. This paper attempts to answer three questions that are being asked with increasing urgency in this setting. First, has the quality of institutions and policies, critical to sustaining higher levels of debt, improved since the debt relief era of the early 2000s? Second, will debt markets get to know emerging Africa well enough before the next crisis? Third, have resolutions of defaults in Africa been orderly so that debtor governments are not herded into traps set by foreign creditors? Our calculations suggest that the answer to all three questions is ‘no’. To avoid another debt crisis, the paper recommends preventive measures. The policy responses involve full transparency in debt accounting, greater realism in growth forecasts and diligence in matching the region’s seemingly limitless public investment needs with limited long-term development finance and weak public-sector capacity to manage infrastructure investments. More specifically, we recommend that African governments treat increases in commodity prices as temporary—not permanent—shocks; that in deciding how to finance public investment, governments compare the marginal cost of funds from taxation with market terms; and that governments not finance long-term infrastructure projects with short-term money from abroad, regardless of the conditions on which these loans can be contracted.
Rembrandt was here
Authors: Campbell Louise 
Published: August 2021

Abstract
In 1911 visitors to the Amsterdam house where Rembrandt lived between 1639 and 1658 were disappointed to find no working studio, bedroom or personal collections. In his design for the Rembrandthuis museum, the architect K.P.C. de Bazel had chosen not to create a period interior, but instead combined domestically scaled rooms with a museum displaying Rembrandt’s prints. The project registered early twentieth-century perceptions of Rembrandt as a modern, and contemporary debates about the restoration of historic buildings. Unlike many nineteenth-century house museums, it was designed to focus attention on the work rather than the life of the occupant. However, in 1998, the museum was reconfigured as a simulacrum of a seventeenth-century house, with a new annex for displaying prints and drawings and for exhibitions. The history of the Rembrandthuis illuminates changing approaches to the artist over time and their implications for architecture and museology in the age of modernism.
Maternal-Offspring Interactions: Reciprocally Coevolving Social Environments
Authors: Wade Michael J 
Published: August 2021

AbstractMaternal-zygotic co-evolution is one of the most common examples of indirect genetic effects. I investigate how maternal-zygotic gene interactions affect rates of evolution and adaptation. Using comparably parameterized population genetic models, I compare evolution to an abiotic environment with genotype-by-environment interaction (G × E) to evolution to a maternal environment with offspring genotype-by-maternal environment interaction (G × Gmaternal). There are strong parallels between the 2 models in the components of fitness variance but they differ in their rates of evolution measured in terms of ∆p, gene frequency change, or of ∆W, change in mean fitness. The Price Equation is used to partition ∆W into 2 components, one owing to the genetic variance in fitness by natural selection and a second owing to change in environment. Adaptive evolution is faster in the 2-locus model with G × Gmaternal with free recombination, than it is in the 1-locus model with G × E, because in the former the maternal genetic environment coevolves with the zygotic phenotype adapting to it. I discuss the relevance of these findings for the evolution of genes with indirect genetic effects.
Novel MRI technique for the quantification of biochemical deterioration in steroid-induced osteonecrosis of femoral head: a prospective diagnostic trial
Authors: Han Xiaorui , Hong Guoju , Guo Yuan , Wu Hongzhen , Sun Ping , Wei Qiushi , Chen Zhenqiu , He Wei , Liu Zaiyi , Liang Changhong 
Published: August 2021

Abstract
To explore the novel magnetic resonance imaging techniques, IVIM-DWI and IDEAL-IQ in detecting bone marrow fat and microcirculation in steroid-induced osteonecrosis of the femoral head (SIONFH). In this prospective study, 49 patients (80 hips) with SIONFH taking glucocorticoids and 24 healthy volunteers (48 hips) were recruited and assessed by T1WI, T2WI/fs, IDEAL-IQ and IVIM-DWI. The affected hips, contralateral asymptomatic hips and normal hips, as well as normal, penumbra and necrotic areas in the affected hips, were classified and evaluated. Imaging results were compared with histologic bone sections obtained from SIONFH patients undergoing surgery. The fat fraction (FF) and perfusion fraction (f) differences between groups were analyzed using analysis of variance, the LSD t-test, Pearson correlation analysis and ROC curve analysis. Our results demonstrate that IDEAL-IQ (FF) and IVIM-DWI (f) enable the classification of SIONFH at different ARCO stages. The FF was positively associated with the progression of the disease (r = 0.72), in contrast to f (r = −0.17). The FF and f were significantly different among the necrotic, penumbra and normal areas, and they were negatively correlated with each other (r = −0.37). The diagnostic sensitivity and specificity of IDEAL-IQ were 96.9% and 86.7%, and those of IVIM-DWI were 72.34% and 58.33%, respectively. The FF in contralateral asymptomatic hips was significantly higher than in normal hips, but no difference was found for f. IDEAL-IQ, and not IVIM-DWI, was identified to successfully detect bone marrow fat, which is beneficial to the diagnosis of the severity of SIONFH.
Toxicity From Blue Lotus (Nymphaea caerulea) After Ingestion or Inhalation: A Case Series
Authors: Schimpf Mackenzie , Ulmer Thomas , Hiller Hugh , Barbuto Alexander F 
Published: August 2021

ABSTRACT
Plant extracts and other novel psychoactives can be ingested, vaped, injected, or insufflated. This includes products such as extracts from the blue lotus flower (Nypmhaea caerulea), which is known to produce euphoria and hallucinations at high doses. Blue lotus is sold in several forms, including dried plant material, teas, and extracts for use in electronic cigarettes. Because newer generations of electronic cigarettes can deliver a variety of substances, practitioners need to be mindful of toxicity from a growing number of psychoactives, some of which are not detectable by standard urine drug screens. This case series describes five active duty patients who presented to the emergency department with altered mental status following the use of blue lotus products, four after vaping and one after making an infused beverage. Patients displayed similar symptoms, including sedation and perceptual disturbances. The patients in our series were successfully managed with supportive measures without the need for sedating agents. Recognizing and identifying new trends in substance use can help to provide directions in undifferentiated altered mental status.
Prospective Evaluation of Health Outcomes in a Nationwide Sample of Aeromedical Evacuation Casualties: Methods From a Pilot Study
Authors: Walker Lauren E , McCabe Cameron T , Watrous Jessica R , Poltavskiy Eduard , Howard Jeffrey T , Janak Jud C , Migliore Laurie , Stewart Ian J , Galarneau Michael R 
Published: August 2021

ABSTRACT

Introduction
Although retrospective analyses have found that combat-injured service members are at high risk for mental and physical health outcomes following injury, relatively little is known about the long-term health of injured service members. To better understand long-term health outcomes after combat injury, a large, prospective observational cohort collecting both subjective and objective health data is needed. Given that a study of this nature would be costly and face many logistical challenges, we first conducted a pilot to assess the feasibility of a larger, definitive study.

Materials and Methods
We ran a prospective, observational pilot study of 119 combat-injured service members and veterans who completed (1) at least one set of laboratory measurements (blood and urine sample collection and vitals measurements) at Clinical Laboratory Improvement Amendment of 1988 compliant laboratory locations and (2) at least one online assessment for the Wounded Warrior Recovery Project (WWRP), a 15-year examination of patient-reported outcomes among service members injured on combat deployment. We recruited the pilot study cohort from WWRP participants who met eligibility criteria and indicated interest in additional research opportunities. We collected laboratory values and patient-reported outcomes at baseline and again 1 year later, and obtained demographic, injury, and military service data from the Expeditionary Medical Encounter Database. The David Grant USAF Medical Center Institution Review Board (IRB) and the Naval Health Research Center IRB reviewed and approved the study protocols.

Results
During recruitment for the pilot study, 624 study candidates were identified from WWRP. Of the 397 candidates we contacted about the pilot study, 179 (45.1%) enrolled and 119 (66.4%) of those who enrolled completed the first year of participation. The second study year was suspended due to the coronavirus disease-2019 pandemic. At the time of suspension, 72 (60.5%) participants completed follow-up laboratory appointments, and 111 (93.3%) completed second-year WWRP assessments. Participants in the pilot study were predominately male (95.0%) and non-Hispanic White (55.5%), with a median (interquartile range) age of 38.3 (34.1-45.4) years.

Conclusions
Collection of patient-reported outcomes and laboratory samples in a geographically dispersed cohort of combat-injured service members is possible. While significant challenges exist, our pilot study results indicate that a larger, longitudinal, cohort study is feasible.
Measuring the vertical response of the Galactic disc to an infalling satellite
Authors: Poggio Eloisa , Laporte Chervin F P , Johnston Kathryn V , D’Onghia Elena , Drimmel Ronald , Grion Filho Douglas 
Published: August 2021

ABSTRACT
Using N-body simulations of the Milky Way interacting with a satellite similar to the Sagittarius dwarf galaxy, we quantitatively analyse the vertical response of the Galactic disc to the satellite’s repeated impacts. We approximate the vertical distortion of the Galactic disc as the sum of the first three Fourier azimuthal terms m = 0, 1, and 2, and observe their evolution in different dynamical regimes of interaction. After the first interaction, the m = 0 term manifests itself as outgoing ring-like vertical distortions. The m = 1 term (S-shape warp) is prograde when the impacts of the satellite are more frequent, or in general close to an interaction, whereas it is slowly retrograde in the most quiescent phases. The m = 2 term is typically prograde, and close to an interaction it couples with the m = 1 term. Finally, we find that the vertical response of the disc can be recovered in an unbiased way using the instantaneous positions and velocities of stars in a limited volume of the Galactic disc, analogous to real data, and that the measured vertical pattern speeds have a constraining power in the context of a Milky Way–satellite interaction.
An optimal non-linear method for simulating relic neutrinos
Authors: Elbers Willem , Frenk Carlos S , Jenkins Adrian , Li Baojiu , Pascoli Silvia 
Published: August 2021

ABSTRACT
Cosmology places the strongest current limits on the sum of neutrino masses. Future observations will further improve the sensitivity and this will require accurate cosmological simulations to quantify possible systematic uncertainties and to make predictions for non-linear scales, where much information resides. However, shot noise arising from neutrino thermal motions limits the accuracy of simulations. In this paper, we introduce a new method for simulating large-scale structure formation with neutrinos that accurately resolves the neutrinos down to small scales and significantly reduces the shot noise. The method works by tracking perturbations to the neutrino phase-space distribution with particles and reduces shot noise in the power spectrum by a factor of $\mathcal {O}\left(10^2\right)$ at z = 0 for minimal neutrino masses and significantly more at higher redshifts, without neglecting the back-reaction caused by neutrino clustering. We prove that the method is part of a family of optimal methods that minimize shot noise subject to a maximum deviation from the non-linear solution. Compared to other methods, we find per mille level agreement in the matter power spectrum and per cent level agreement in the large-scale neutrino bias, but large differences in the neutrino component on small scales. A basic version of the method can easily be implemented in existing N-body codes and allows neutrino simulations with significantly reduced particle load. Further gains are possible by constructing background models based on perturbation theory. A major advantage of this technique is that it works well for all masses, enabling a consistent exploration of the full neutrino parameter space.
Linking Uranus’ temperature profile to wind-induced magnetic fields
Authors: Soyuer Deniz , Helled Ravit 
Published: August 2021

ABSTRACT
The low luminosity of Uranus is still a puzzling phenomenon and has key implications for the thermal and compositional gradients within the planet. Recent studies have shown that planetary volatiles become ionically conducting under conditions that are present in the ice giants. Rapidly growing electrical conductivity with increasing depth would couple zonal flows to the background magnetic field in the planets, inducing poloidal and toroidal field perturbations $\boldsymbol {B}^{\omega } = \boldsymbol {B}^{\omega }_\mathrm{ P} + \boldsymbol {B}^{\omega }_\mathrm{ T}$ via the ω-effect. Toroidal perturbations $\boldsymbol {B}^{\omega }_\mathrm{ T}$ are expected to diffuse downwards and produce poloidal fields $\boldsymbol {B}^{\alpha }_\mathrm{ P}$ through turbulent convection via the α-effect, comparable in strength to those of the ω-effect, $\boldsymbol {B}^{\omega }_\mathrm{ P}$. To estimate the strength of poloidal field perturbations for various Uranus models in the literature, we generate wind decay profiles based on Ohmic dissipation constraints assuming an ionically conducting H2–He–H2O interior. Because of the higher metallicities in outer regions of hot Uranus models, zonal winds need to decay to ∼0.1 per cent of their surface values in the outer 1 per cent of Uranus to admit decay solutions in the Ohmic framework. Our estimates suggest that colder Uranus models could potentially have poloidal field perturbations that reach up to $\mathcal {O}(0.1)$ of the background magnetic field in the most extreme case. The possible existence of poloidal field perturbations spatially correlated with Uranus’ zonal flows could be used to constrain Uranus’ interior structure, and presents a further case for the in situ exploration of Uranus.
81 New candidate fast radio bursts in Parkes archive
Authors: Yang X , Zhang S-B , Wang J-S , Hobbs G , Sun T-R , Manchester R N , Geng J-J , Russell C J , Luo R , Tang Z-F , Wang C , Wei J-J , Staveley-Smith L , Dai S , Li Y , Yang Y-Y , Wu X-F 
Published: August 2021

ABSTRACT
We have searched for weak fast radio burst (FRB) events using a data base containing 568 736 756 transient events detected using the Parkes radio telescope between 1997 and 2001. In order to classify these pulses, and to identify likely FRB candidates, we used a machine-learning algorithm based on ResNet. We identified 81 new candidate FRBs and provide details of their positions, event times, and dispersion measures. These events were detected in only one beam of the Parkes multibeam receiver. We used a relatively low S/N cut-off threshold when selecting these bursts and some have dispersion measures only slightly exceeding the expected Galactic contribution. We therefore present these candidate FRBs as a guide for follow-up observations in the search for repeating FRBs.