bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neutron star outer crust equation of state: a machine learning approach
Authors: Murarka Utsav , Banerjee Kinjal , Malik Tuhin , Providência Constança 
Published: January 2022

Abstract
Constructing the outer crust of the neutron stars requires the knowledge of the Binding Energy (BE) of the atomic nuclei. Although the BE of a lot of the nuclei is experimentally determined and can be obtained from the AME data table, for the others we need to depend on theoretical models. There exist a lot of physical theories to predict the BE, each with its own strengths and weaknesses. In this paper we apply Machine Learning (ML) algorithms on AME2016 data set to predict the Binding Energy of atomic nuclei. The novel feature of our work is that it is model independent. We do not assume or use any nuclear physics model but use only ML algorithms directly on the AME2016 data set. Our results are further refined by using another ML algorithm to train the errors of the first algorithm, and repeating this process iteratively. Our best algorithm gives σrms ∼ 0.58 MeV for Binding Energy on randomized testing sets. This is comparable to all physics models or ML improved physics models studied in literature till date. Using the predictions of our Machine Learning algorithm, we construct the outer crust equation of state (EoS) of a neutron star and show that our model is comparable to existing models. This work also demonstrates the use of various ML algorithms and a detailed analysis on how we arrived at our best algorithm. It will help the physics community in understanding how to choose an ML algorithm which would be suited for their data set. Our algorithms and best fit model is also made publicly available for the use of the community.
Primary aberrations in tightly focused polarized anomalous vortex beams
Authors: Xu Menghua , Qin Yali , Ji Kailai , Zhang Hongshun 
Published: January 2022

Abstract
Based on the Richards Wolf vector diffraction theory, the intensity profiles of the radially and azimuthally polarized anomalous vortex beams focused by a high numerical aperture (NA) lens in the presence of primary aberration are obtained. The effects of the primary aberration coefficient on the intensity distribution, longitudinal field and the quality of the aberrated focused field through calculating the Strehl ratio under various polarized input beams are analyzed. The results show that spherical aberration destroys the rotational symmetry of the focused intensity about the optical axis. Coma will shift the focal spot which gradually presents an obvious comet shape. Astigmatism will elongate the focal spot. Meanwhile, defocus technology on compensating aberrations is studied. The results have potential applications in the design and assembly of high NA systems or overcoming aberrations in the future.
Monte Carlo study of plastic rod scintillators for use in industrial computed tomography
Authors: Taheri A. , Askari M. 
Published: January 2022

Abstract
Industrial gamma-ray computed tomography systems have found different applications and have become an important tool for non-destructive testing. In this work, high aspect ratio rod plastic scintillators were assessed for use in this type of tomography system. All analyses were performed using Monte Carlo simulation by geant4 toolkit. Validation of the results was done using a 50 cm rod plastic scintillator with a diameter of 5 cm. The results showed that the rod plastic scintillators can be employed in industrial tomography systems for scanning large objects. The spatial resolution of the detection system was estimated more than 1 cm. Finally, the simulated parameters of the selected rod plastic scintillator were compared with an identical NaI(Tl) rod scintillator to find a better understanding about its performance.
Estimating heat-related mortality in near real time for national heatwave plans
Authors: Lo Y T Eunice , Mitchell Dann M , Thompson Ross , O’Connell Emer , Gasparrini Antonio 
Published: January 2022

Abstract
Heatwaves are a serious threat to human life. Public health agencies that are responsible for delivering heat-health action plans need to assess and reduce the mortality impacts of heat. Statistical models developed in epidemiology have previously been used to attribute past observed deaths to high temperatures and project future heat-related deaths. Here, we investigate the novel use of summer temperature-mortality associations established by these models for monitoring heat-related deaths in regions in England in near real time. For four summers in the period 2011–2020, we find that coupling these associations with observed daily mean temperatures results in England-wide heatwave mortality estimates that are consistent with the excess deaths estimated by UK Health Security Agency. However, our results for 2013, 2018 and 2020 highlight that the lagged effects of heat and characteristics of individual summers contribute to disagreement between the two methods. We suggest that our method can be used for heatwave mortality monitoring in England because it has the advantages of including lagged effects and controlling for other risk factors. It could also be employed by health agencies elsewhere for reliably estimating the health burden of heat in near real time and near-term forecasts.
Permutation invariant Gaussian two-matrix models
Authors: Barnes George , Padellaro Adrian , Ramgoolam Sanjaye 
Published: January 2022

Abstract
We construct the general permutation invariant Gaussian two-matrix model for matrices of arbitrary size D. The parameters of the model are given in terms of variables defined using the representation theory of the symmetric group S

D
. A correspondence is established between the permutation invariant polynomial functions of the matrix variables (the observables of the model) and directed colored graphs, which sheds light on stability properties in the large D counting of these invariants. A refined counting of the graphs is given in terms of double cosets involving permutation groups defined by the local structure of the graphs. Linear and quadratic observables are transformed to an S

D
representation theoretic basis and are used to define the convergent Gaussian measure. The perturbative rules for the computation of expectation values of graph-basis observables of any degree are given in terms of the representation theoretic parameters. Explicit results for a number of observables of degree up to four are given along with a Sage programme that computes general expectation values.
Bisulfite-initiated crosslinking of gelatin methacryloyl hydrogels for embedded 3D bioprinting
Authors: Bilici Çiğdem , Tatar Asena G , Şentürk Efsun , Dikyol Caner , Koç Bahattin 
Published: January 2022

Abstract
Recent studies on three-dimensional (3D) bioprinting of cell-laden gelatin methacryloyl (GelMA) hydrogels have provided promising outcomes for tissue engineering applications. However, the reliance on the use of photo-induced gelation processes for the bioprinting of GelMA and the lack of an alternative crosslinking process remain major challenges for the fabrication of cell-laden structures. Here, we present a novel crosslinking approach to form cell-laden GelMA hydrogel constructs through 3D embedded bioprinting without using any external irradiation that could drastically affect cell viability and functionality. This approach consists of a one-step type of crosslinking via bisulfite-initiated radical polymerization, which is combined with embedded bioprinting technology to improve the structural complexity of printed structures. By this means, complex-shaped hydrogel bio-structures with cell viability higher than 90% were successfully printed within a support bath including sodium bisulfite. This study offers an important alternative to other photo-induced gelation processes to improve the bio-fabrication of GelMA hydrogel with high cell viability.
High energy electron beam generation during interaction of a laser accelerated proton beam with a gas-discharge plasma
Authors: XU Wangwen , HU Zhanghu , HUI Dexuan , WANG Younian 
Published: January 2022

Abstract
The study of the interaction between ion beam and plasma is very important to the areas of inertial fusion energy and high energy density physics. With detailed one-dimensional electromagnetic particle-in-cell simulations, we investigate here the interaction of a laser-accelerated proton beam assuming an ideal monoenergetic beam with a gas-discharge plasma. After the saturation stage of the two-stream instability excited by the proton beam, significant high energy electrons are observed, with maximum energy approaching 2 MeV, and a new two-stream instability occurs between the high energy electrons and background electrons. The trajectories of plasma electrons are studied, showing the process of electron trapping and de-trapping from the wakefield.
OP01 Withdrawal of infliximab or anti-metabolite therapy in Crohn’s Disease patients in sustained remission on combination therapy: A randomized unblinded controlled trial (SPARE)
Authors: Louis J E , Resche-Rigon M , Laharie D , Satsangi J , Ding N , Preiss J , D’Haens G , Picon L , Bossuyt P , Vuitton L , Irving P , Bouhnik Y , Viennot S , Lamb C , Pollock R , Baert F , Nachury M , Mathurin F , Gilletta C , Colombel J F , Hertervig E 
Published: January 2022

Abstract

Background
Combination therapy with infliximab and anti-metabolites is a standard option for patients with Crohn’s disease (CD). The implications of long term use of combination therapy may lead patients and clinicians to contemplate treatment de-escalation once steroid-free remission has been achieved. The aim of our study was to assess the relapse rates and time spent in remission over 2 years, after withdrawal of infliximab or anti-metabolite compared to continuation of combination therapy.

Methods
CD patients treated with a combination therapy of infliximab (IFX) and anti-metabolite &gt; 8 months and in sustained steroid-free remission &gt; 6 months were recruited in 64 centers in France, United Kingdom, Belgium, Sweden, Australia, Germany and The Netherlands. Patients were randomized into 3 arms - continuing combination therapy (arm A); stopping IFX (arm B); or stopping anti-metabolite (arm C). In case of a relapse [defined by CDAI and an objective marker of inflammation (CRP or fecal calprotectin)], patients were retreated by resuming infliximab in arm B or the anti-metabolite in arm C, according to a pre-defined scheme, including optimization of IFX up to 10 mg/Kg if necessary in all arms. The two co-primary endpoints were the relapse rate and mean survival time spent in remission over 2 years. A major secondary endpoint was treatment failure (complications or not recapturing remission).

Results
254 patients were screened, 211 randomized, 5 withdrew consent and 1 was lost to follow-up, leaving 205 patients for the analysis - 67 randomized to arm A, 71 to arm B and 67 to arm C. Demographic and clinical characteristics are shown in Table 1. The two-year relapse rates were 14% (IC95%: 4–23%) in arm A, 40% (IC95%: 28–51%) in arm B, and 10% (IC95%: 2–18%) in arm C (p=0.0003 arm B vs arm A and &lt;0.0001 arm B vs arm C) (figure 1). The time spent in remission was 1.91 yrs (IC95%: 1.83–1.99), 1.89 yrs (IC95%: 1.82–1.96) and 1.93 yrs (IC95%: 1.86–2.00) in arm A, B and C, respectively. Out of the 39 relapsers, 28 were retreated/optimized. Remission was achieved in 1/2 retreated patients in arm A, 22/23 in arm B and 2/3 in arm C. Treatment failure was observed in 4/67, 4/71 and 3/67 patients, in these three arms, respectively. No malignancy was observed, one tuberculosis in arm C and two severe infections (pneumonia and viral pericarditis) in arm B.

Conclusion
Infliximab withdrawal, but not antimetabolite withdrawal, was associated with a significantly higher risk of relapse than continuation of combination therapy. Almost all patients who stopped IFX achieved rapid remission when resuming treatment. The time spent in remission over 2 years was similar across groups.
OP18 Efficacy and safety of filgotinib for the treatment of perianal fistulizing Crohn’s Disease: Results from the phase 2 DIVERGENCE 2 study
Authors: Reinisch W , Colombel J F , D’Haens G R , Rimola J , DeHaas-Amatsaleh A , McKevitt M , Ren X , Serone A , Schwartz D A , Gecse K B 
Published: January 2022

Abstract

Background
Treatment of perianal fistulizing Crohn’s disease (PFCD) is a major unmet need. Filgotinib (FIL) is a once-daily, oral, preferential Janus kinase 1 inhibitor in development for the treatment of inflammatory bowel diseases. The efficacy and safety of FIL for the treatment of PFCD was evaluated in the phase 2, double-blind, randomized, placebo (PBO)-controlled DIVERGENCE 2 study (NCT03077412).

Methods
Patients (18–75 years old) with PFCD (documented diagnosis of CD for at least 3 months and 1–3 external openings [EOs] with drainage [spontaneous or on compression] for ≥ 4 weeks before screening) previously treated with antibiotics, immunomodulators and/or tumour necrosis factor inhibitors (TNFi) were randomized (2:2:1) to receive FIL 200 mg, FIL 100 mg or PBO once daily for up to 24 weeks. Active luminal CD was permitted providing that the Crohn’s Disease Activity Index score was ≤ 300 at screening. The primary endpoint was combined fistula response (reduction of ≥ 1 from baseline in the number of draining EOs determined by investigator assessment and no fluid collections &gt; 1 cm on centrally read pelvic magnetic resonance imaging [MRI]) at Week 24. Combined fistula remission (closure of all draining EOs present at baseline and no fluid collections &gt; 1 cm) at Week 24 was a key secondary endpoint. The study was not powered for statistical comparisons and was prematurely terminated owing to low recruitment rates during the COVID-19 pandemic.

Results
Baseline characteristics were broadly similar across the treatment groups (Table 1). Overall, 91.2% of patients had complex perianal fistulae and TNFi treatment had previously failed in 64.9% of patients. A lower proportion of patients randomized to receive FIL 200 mg discontinued the study compared with those who received PBO (Table 2). The proportion of patients who achieved a combined fistula response at Week 24 was numerically higher in the FIL 200 mg group (47.1%; 90% confidence interval [CI]: 26.0–68.9) than in the PBO group (25.0%; 90% CI: 7.2–52.7) (Figure 1), with similar results observed for combined fistula remission (FIL 200 mg [47.1%; CI: 26.0–68.9] versus PBO [16.7%; CI: 3.0–43.8]) (Figure 2). Treatment-emergent severe adverse events were highest in the FIL 200 mg group (Table 2). Adverse event rates were otherwise similar across treatment groups.

Conclusion
In this phase 2 study, numerically higher fistula response and remission rates were observed after 24 weeks of treatment with FIL 200 mg versus PBO in patients with active PFCD and a history of multiple medical treatment failures. FIL was well tolerated overall. Further studies of FIL for the treatment of PFCD are warranted.
DOP15 Fluorescent labelled vedolizumab for real-time visualization and quantification of local drug distribution and pharmacodynamics in Inflammatory Bowel Diseases during endoscopy
Authors: Gabriëls R Y , Linssen M , van der Waaij A , Volkmer P , Hooghiemstra W , Kats-Ugurlu G , Robinson D , Dijkstra G , Nagengast W 
Published: January 2022

Abstract

Background
Vedolizumab is a monoclonal antibody which blocks integrin α4β7 inhibiting trafficking of T-lymphocytes into the gut. Unfortunately, up to 60% of vedolizumab patients experience non-response. The mechanism of action of vedolizumab is not elucidated, predictors of response are unknown and data for local drug distribution in the gut are lacking. In this clinical trial, we investigated the feasibility of assessing local distribution of fluorescently labelled vedolizumab in the gut mucosa of inflammatory bowel diseases (IBD) patients to finally enable prediction of therapy response in individual patients.

Methods
Vedolizumab (Entyvio, Takeda Pharma) was labelled to IRDye 800CW under cGMP conditions to yield clinical grade vedolizumab-800CW. In this dose-escalation trial, vedolizumab naïve IBD patients and IBD patients treated with vedolizumab for at least 14 weeks were included. Patients received an intravenous dose of fluorescently labelled vedolizumab of either 0 mg, 4.5 mg, 15 mg or 15 mg + 75 mg unlabelled vedolizumab 3 days prior colonoscopy. In vivo fluorescence imaging was assessed by fibre-based wide-field fluorescence molecular endoscopy (FME) and quantified by spectroscopy in healthy, mildly inflamed and severely inflamed tissue. All assessed tissue was biopsied for ex vivo examination of the fluorescent signal, fluorescence microscopy and spectroscopy.

Results
Up to submission 34 patients completed tracer injection and FME. An interim analysis was performed after 20 patients (5 in each dose group), which showed in severely inflamed tissue an 8 fold higher fluorescent signal in the 15 mg dose group (0.049 Q*μfa,x [mm-1]) compared to the control group (0.006 μfa,x [mm-1]) (p&lt;0.05). Furthermore, the fluorescent signal within the 15 mg dose group was also 2.5 fold higher compared to healthy tissue (0.019 Q*μfa,x [mm-1]) (p&lt;0.05).The addition of unlabelled vedolizumab gave similar results to the 15 mg group (p&gt;0.99), suggesting that the drug target was still not saturated. The optimal dosage group of 15 mg was expanded up to 18 IBD patients, amongst them 6 IBD patients after 14 weeks of treatment regimen. Fluorescence microscopy showed clustering of fluorescent signals especially in inflamed mucosa. Additional experiments to detect vedolizumab target cells are ongoing.

Conclusion
In vivo visualization of fluorescent vedolizumab revealed a clear dose-dependent correlation between mucosal drug concentrations and the severity of mucosal inflammation. Fluorescence molecular endoscopy is a promising novel tool to get insight in drug distribution in IBD, detect target cells, assess target engagement and possibly predict therapy response in individual patients.
DOP54 Identification and development of a 1st in class naturally-derived protein that drives mucosal healing and is orally delivered by an engineered cellular therapy targeting the gastro-intestinal tract
Authors: Shilova I , La Chat C , Nigatu E , Messner E , Desnoyer J , Willcoxon M , Banas S , Ravichandar D , Narayan N , DeSantis T , Dabbagh K , Yamamoto L 
Published: January 2022

Abstract

Background
In Inflammatory Bowel Disease (IBD), intestinal barrier dysfunction and epithelial cell injury are believed to be associated with activation of the immune system to drive disease-associated inflammation, which together constitute key features of active disease. Existing drugs used to treat IBD induce endoscopic remission and improvements in mucosal healing in only a minor proportion of patients, driving a critical need for therapies which lead directly to mucosal healing. Furthermore, predicting patients who may benefit from therapeutics that address specific mechanisms of mucosal healing may augment response rates.

Methods
We screened proteins, identified from a meta-analysis of healthy human microbiome, in cellular assays and animal models related to mucosal injury, with the goal of identifying novel therapeutics that have the potential to directly induce mucosal healing. The proteins identified were further optimized by protein engineering to increase their stability as well as gastro-intestinal (GI) targeting via oral administration. For this, therapeutic proteins were expressed using a probiotic, Lactococcus lactis (L.lactis), engineered to display the recombinant proteins on the cell surface, and evaluated for activity in DSS- and DNBS-induced models of colitis in mice. Mechanism of action studies using computational and laboratory based methods to analyze gene expression and direct molecular interactions with human proteins, enabled the identification of pathways modulated by the candidate molecules. These pathways were further evaluated for their ability to identify biomarkers in specific patients most suitable for treatment in a precision medicine approach.

Results
We have identified a novel, healthy microbiome-derived protein that demonstrated robust activity in human epithelial injury assays in vitro. The protein reduced intestinal injury related pathology in mice when orally administered to target directly the GI tract. SG-5-00455, the product based on an L.lactis strain expressing the candidate therapeutic protein, reduced pathology scores, inflammation and barrier function related LPS-binding protein levels to levels comparable to those obtained glucagon-like peptide 2 (GLP-2), as well as improving dysregulated tissue repair and fibrosis-associated gene expression and proteins levels. SG-5-0455 treatment did not result in systemic exposure, driving its therapeutic activity in a GI-localized manner by targeting pathways related to tissue injury and fibrinolysis.

Conclusion
SG-5-00455, through its novel mechanism of action and oral delivery to directly target tissue repair pathways in the GI-tract, offers the potential to address a large critical need in IBD.
DOP85 Efficacy of risankizumab rescue therapy in patients with moderately to severely active Crohn’s Disease and inadequate response to risankizumab maintenance therapy
Authors: Baert F J , Atreya R , Kakuta Y , Long M , Roblin X , Neimark E , Song A , Wallace K , Kingys K , Mallick M , Liao X , Lim A 
Published: January 2022

Abstract

Background
The efficacy and safety of 12 weeks of induction and 52 weeks of maintenance treatment with risankizumab (RZB), an interleukin 23 p19 inhibitor, in patients with moderately to severely active Crohn’s disease (CD) was previously demonstrated in 3 phase 3 trials (ADVANCE, MOTIVATE, and FORTIFY). We investigated outcomes in patients with inadequate response to subcutaneous (SC) RZB or SC placebo (PBO) treatment and required RZB rescue therapy during maintenance.

Methods
In FORTIFY, a phase 3, double-blind, re-randomised responder withdrawal, maintenance study (NCT03105102), patients that responded to 12 weeks of RZB IV induction received RZB 180 mg SC, RZB 360 mg SC, or PBO (ie, withdrawal) every 8 weeks for 52 weeks. Starting at week 16, patients with inadequate response, defined as average daily stool frequency [SF] ≥ 3.3 and/or average daily abdominal pain score [APS] ≥ 1.5 as well as high-sensitivity C-reactive protein ≥ 5 mg/L and/or faecal calprotectin ≥ 250 μg/g; or Simple Endoscopic Score for CD (SES-CD) ≥ 6 (≥ 4 for isolated ileal disease), excluding the narrowing component as scored by the site Investigator, were eligible to receive open-label rescue therapy (1 dose of intravenous [IV] RZB 1200 mg, followed by RZB 360 mg SC every 8 weeks). Up to 2 rescue therapy visits ≥ 16 weeks apart were permitted. Efficacy at week 52 was assessed in the intent-to-treat population using nonresponder imputation for missing data. Patients were also considered nonresponders when maximum equivalent steroid dose exceeded the dose used at baseline or if patients initiated any new steroids. Safety was assessed throughout the study.

Results
In the maintenance study, a greater proportion of patients in the withdrawal (PBO SC) arm (40.2% [66/164]) were administered RZB rescue therapy vs RZB 180 mg SC (24.2% [38/157]) and RZB 360 mg SC (21.3% [30/141]; Figure A); most patients (71.1%–81.8%) required 1 rescue visit, and 16.7%–26.3% required 2 visits. Median time to first RZB rescue therapy was 178 days for the withdrawal (PBO SC) group, 179 days for the RZB 180 mg SC group, and 154 days for the RZB 360 mg SC group. At week 52, 52.5%–75.0% of patients who received RZB rescue therapy achieved SF/APS clinical response (Figure B), and 20.0–36.4% of patients who received rescue therapy achieved clinical remission (per CDAI or SF/APS) and/or endoscopic response (Figures C-E). The safety profile of RZB in CD has previously been reported.

Conclusion
RZB rescue therapy (one dose of RZB 1200 mg IV followed by RZB 360 mg SC every 8 weeks) may be beneficial to patients with moderately to severely active CD experiencing inadequate response to or interruption in RZB maintenance treatment.