bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling light wave propagation and interaction and dynamical regimes analysis using the Lyapunov exponents method in ring fibre cavities
Authors: Razukov V A , Melnikov L A , Kuptsov P V , Gochelashvili K S
Published: January 2023

The ‘Cabaret’ finite differences method allows the performance of fast and conclusive modelling of the microcavity temporal dynamics with group velocity dispersion, cross- and self- phase modulation included. The proposed scheme and model allow us to study the dynamics of a cavity with two counter-propagating pulses, second order dispersion, modulation instability, Rayleigh scattering and other effects along the cavity roundtrips number up to 106…7. The possibility of Lyapunov exponents mapping for the Raman and SBS fibre lasers and cavities is discussed.
The influence of time varying magnetic fields on the determinations of Newton’s constant at the Bureau International des Poids et Mesures
Authors: Speake Clive C , Bryant John L , Davis Richard S , Quinn Terry J
Published: January 2023

The values of Newton’s constant of gravitation, G, reported by determinations at the International Bureau of Weights and Measures (BIPM) in Quinn et al (2001 Phys. Rev. Lett.
87 111101/1–111101/4) and in Quinn et al (2013 Phil. Trans. R. Soc. A
372 2–28) are some 200 parts per million (ppm) larger than the value of

6.67430
×

10

−
11

m3 kg−1 s−2 which was recommended by CODATA in Tiesinga et al (2018 J. Phys. Chem. Ref. Data
50 033105). The CODATA value has an assigned uncertainty of 22 ppm and the reported uncertainties in the BIPM values were 41 ppm and 25 ppm, respectively. The discrepancy therefore amounts to about seven times the combined uncertainty of the latest BIPM and CODATA values. We examine experimentally the hypothesis that the difference is due to a bias produced by stray alternating (AC) magnetic fields in the vicinity of the experiment. Whilst the BIPM torsion balance was located at the University of Birmingham a coil, having a similar scale to the balance, was used to generate AC magnetic fields of magnitude approximately 1 μT which in turn produced torques of magnitude approximately 0.2 % of the gravity torque. The magnitudes of these torques were compared with simple analytical models and finite element analyses. Measurements in the laboratory in Birmingham and, more recently, at BIPM give a very conservative upper limit on the rms magnitude of ambient AC magnetic fields of 100 nT. As the torque was demonstrated to vary with the square of the ambient field, these observations and our analyses suggest an upper limit to the possible bias in the BIPM determinations of the order of 20 ppm. It is therefore unlikely that torques due to ambient magnetic fields could have significantly biased values of G determined at BIPM.
Influence of pulsed TIG welding process parameters on the mechanical characteristics of AA5083 with AA6082 weldments
Authors: A Ramarajan , Jayakumar K
Published: January 2023

Aluminium alloys have been widely accepted in manufacturing lightweight materials with high strength. Therefore, welding aluminium alloys is essential in industrial applications to attain complex shapes. In the present work, AA5083 and AA6082 dissimilar alloys were welded using pulsed tungsten inert gas (PTIG) welding since PTIG reduces welding defects more than TIG welding. But to get better mechanical strength on the weld joints, PTIG welding process parameters must be optimized. During PTIG welding, peak current, pulse frequency, and welding speed were chosen as the input parameters, and ultimate tensile strength (UTS) and microhardness were measured as output responses in the current investigation. The UTS of the welded AA5083-AA6082 alloys was predicted using an empirical relationship. For the design of experimental trials, a three-variable, five-stage central composite design is adopted. The findings indicate that the welding speed impacts tensile strength the most, followed by the peak current and the pulse frequency has the least impact. Therefore, the peak current of 197 A, pulse frequency of 4.9 Hz, and welding speed of 181 mm min−1 was identified as the optimal welding parameters to weld AA5083 and AA6082 alloys with high UTS values. The hardness analysis on the optimized welded samples showed that the lowest hardness values of 40 to 50 Hv0.5 and the highest value of 90 to 100 Hv0.5 were observed on the HAZ of the AA6082 side of the weldment.
A Fourier-transformed feature engineering design for predicting ternary perovskite properties by coupling a two-dimensional convolutional neural network with a support vector machine (Conv2D-SVM)
Authors: Chenebuah Ericsson Tetteh , Nganbe Michel , Tchagang Alain Beaudelaire
Published: January 2023

In computational material sciences, Machine Learning (ML) techniques are now competitive alternatives that can be used in determining target properties conventionally resolved by ab initio quantum mechanical simulations or experimental synthesization. The successes realized with ML-based techniques often rely on the quality of the design architecture, in addition to the descriptors used in representing a chemical compound with good target mapping property. With the perovskite crystal structure at the forefront of modern energy materials discovery, accurately estimating related target properties is even of high importance due to the role such properties may have in defining the functionalization. As a result, the present study proposes a new feature engineering approach that takes advantage of both the direct ionic features and the periodic Fourier transformed reciprocal features of a three-dimensional perovskite polyhedral. The study is conducted on about 27,000 ABX3 perovskite structures with the stability energy, the formation energy, and the energy bandgap as targets. For accurate modeling, a feature-extracting two-dimensional convolutional neural network (Conv2D) is coupled with a prediction-enhancing Support Vector Machine (SVM) to form a hybridized Conv2D-SVM architecture. A comparison with previous benchmark evaluations reveals appreciable improvements in modeling accuracy for all target properties, particularly for the energy bandgap, for which the feature extraction approach yields 0.105 eV MAE, 0.301 eV RMSE, and 93.48% R2. Besides, the proposed design is further demonstrated to out-perform other similar periodic feature engineering approaches in the Coulomb matrix, Ewald-sum matrix, and Sine matrix, all in their absolute eigenvalue forms. All preprocessed data, source codes, and relevant sample calculations are openly available at: github.com/chenebuah/high_dim_descriptor.
First principles study of Ti-Zr-Ta alloy phase stability and elastic properties
Authors: Ruobing Zhang , Lin Ai
Published: January 2023

The effects of Ta and Zr content on the stability, elastic properties and electronic structure of Ti-Zr-Ta alloy phase were studied by first principles calculation method based on density functional theory. Moreover, Ti-Zr-Ta alloy was fabricated by spark plasma sintering (SPS) using spherical Ti powder,Ta powder, and Ti-Zr-Ta alloy powder produced by the plasma rotation electrode process (PREP). Afterward, the effects of sintering temperature, Zr and Ta content on the microstructure and mechanical properties of the alloy samples were investigated. The results showed that sintering temperature, Ta and Zr content were the key factors which affected the densification. When the sintering temperature was raised, the relative density and mechanical properties of Ti-Zr-Ta alloy were significantly increased. The first- principles calculation also indicated that Ti-1Zr-Ta possesses the lowest Young’s modulus and the best ductility, showing great potential of biomedical applications which agrees with the results of experimental results of alloy preparation.
Water demands of permitted and unpermitted cannabis cultivation in Northern California
Authors: Dillis Christopher , Butsic Van , Georgakakos Phillip , Portugal Elijah , Grantham Theodore E
Published: January 2023

Illicit water use for irrigated agriculture can have substantial impacts on the environment and complicates water management decision-making. Water demand for illicit cannabis farming in California has long been considered a threat to watershed health, yet an accounting of cannabis irrigation has remained elusive, thereby impeding effective water policy for the state’s nascent legal cannabis industry. Using data obtained from both permitted and unpermitted cultivation operations, the current study applies novel water-use models to cannabis farms in Northern California to estimate their cumulative and relative water footprints. Our results indicated substantial variation in total water extraction volumes for cannabis farming between watersheds and that most cannabis water use was concentrated in a subset of watersheds, rather than evenly spread across the landscape. Water extraction volumes for unpermitted cannabis were consistently greater than permitted cannabis in the dry season, when streams are most vulnerable to impacts from water diversions. Results from scenario modeling exercises indicated that if all existing unpermitted farms were to become permitted and comply with regulations that prohibit surface water diversions in the dry season, nearly one third (34 of 115) of the study watersheds would experience a 50% reduction in dry season water extraction. In comparison, modest expansion of off-stream storage by all cannabis farms could reduce dry season extraction by 50% or greater in more than three quarters (96 of 115) of study watersheds. Combining diversion limits with enhanced storage could achieve dry season extraction reductions of 50% or greater in 100 of 115 watersheds. Our findings suggest that efforts to address the environmental impacts of unpermitted cultivation should focus on watersheds with greatest water demands and that programs that support expansion of off-stream storage can be helpful for reducing pressures on the environment and facilitating the transition of unpermitted farms to the regulated market.
Process optimization and simulation of biodiesel synthesis from waste cooking oil through supercritical transesterification reaction without catalyst
Authors: Ahmed Anas , Ali Abulhassan , Mubashir Muhammad , Lim Hooi Ren , Khoo Kuan Shiong , Show Pau Loke
Published: January 2023

This study reports optimization and simulation of biodiesel synthesis from waste cooking oil through supercritical transesterification reaction without the use of any catalyst. Although the catalyst enhances the reaction rate but due to the presence of water contents in waste cooking oil, the use of catalyst could cause a negative impact on the biodiesel yield. The transesterification reaction without catalyst also offers the advantage of the reduction of pretreatment cost. This study comprises of two steps; first step involves the development and validation of process simulation scheme. The second step involves the optimization using Response Surface Methodology. Face-centered central composite design of experiments is used for experimental matrix development and subsequent statistical analysis of the results. Analysis of variance (ANOVA) is employed for optimization purpose. In addition, a sensitivity study of the process parameters including pressure, temperature, and molar ration of oil-to-methanol was conducted. The statistical analysis reveals that temperature is the most influential process parameter as compared to pressure and oil-to-methanol molar ratio. The optimization study results in the maximum biodiesel yield (94.16%) at an optimum temperature of 274.8°C, 7.02 bar pressure, and an oil-to-methanol molar ratio of 12.43.
Performance and application of Si/Ti3C2T
x
(MXene) composites in lithium ion battery
Authors: Jiang Tingting , Xiong Qilun , Yang Hao , Chen George Z
Published: January 2023

The excellent theoretical specific charge (lithium) storage capacity and rich abundance of silicon (Si), and the good mechanical and electrical properties of titanium based MXene (Ti3C2T
x
) nanosheets promise high performance composites (Si/Ti3C2T
x
) for negative electrodes (negatrodes) in future lithium ion battery (LIB) applications. In particular, the Si/Ti3C2T
x
composites have been preliminarily shown to offer large and stable cyclic capacity, good rate capability and a highly profitable market prospect. To better understand and help further improve the electrochemical performance of these composites, this review focuses on the electrochemical processes occurring in Si/MXene composites from a material perspective. Different cells used for electrochemical measurements, the related materials properties and the reaction processes and kinetics of Si/MXene composites as negatrode in LIB are reviewed. The perspective is also discussed for practical applications in flexible electronic devices and automobiles.
Autonomous victim detection system based on deep learning and multispectral imagery
Authors: Cruz Ulloa Christyan , Garrido Luis , del Cerro Jaime , Barrientos Antonio
Published: January 2023

Post-disaster environments resulting from catastrophic events, leave sequels such as victims trapped in debris, which are difficult to detect by rescuers in a first inspection. Technological advances in electronics and perception have allowed the development of versatile and powerful optical sensors capable of capturing light in spectrums that humans cannot. new deep learning techniques, such as convolutional neural networks (CNNs), has allowed the generation of network models capable of autonomously detecting specific image patterns according to previous training. This work introduces an autonomous victim detection system to be deployed by using search and rescue robots. The proposed system defines new indexes based on combining the multispectral bands (Blue, Green, Red, Nir, Red Edge) to obtain new multispectral images where relevant characteristics of victims and the environment are highlighted. CNNs have been used as a second phase for automatically detecting victims in these new multispectral images. A qualitative and quantitative analysis of new indexes proposed by the authors has been carried out to evaluate their efficiency in contrast to the state-of-the-art ones. A data set has been generated to train different CNN models based on the best obtained index to analyze their effectiveness in detecting victims. The results show an efficiency of 92% in automatically detecting victims when applying the best multispectral index to new data. This method has also been contrasted with others based on thermal and RGB imagery to detect victims, where it has been proven that it generates better results in situations of outdoor environments and different weather conditions.
Environmental Virtue Aesthetics
Authors: Hall Nicole , Brady Emily
Published: January 2023

How should we characterize the interaction between moral and aesthetic values in the context of environmental aesthetics? This question is important given the urgency of many environmental problems and the particular role played by aesthetic value in our experience of environment. To address this question, we develop a model of Environmental Virtue Aesthetics (EVA) that, we argue, offers a promising alternative to current theories in environmental aesthetics with respect to the relationship between aesthetics and ethics. EVA counters environmental aesthetic theories that focus more narrowly on scientific knowledge and ground aesthetic value in ways that obfuscate pluralistic modes of appreciation of and relationships with natural and semi-natural environments. To develop EVA, we work with a revised notion of respect and engage with ideas concerning the development of aesthetic sensibilities, care, and virtuous aesthetic appreciation. EVA has the potential to support forms of human-nature co-flourishing, as well as constituting an aesthetic grounding for ecological citizenship.
Comparison of falls and cost-effectiveness of the group versus individually delivered Lifestyle-integrated Functional Exercise (LiFE) program: final results from the LiFE-is-LiFE non-inferiority trial
Authors: Jansen Carl-Philipp , Gottschalk Sophie , Nerz Corinna , Labudek Sarah , Kramer-Gmeiner Franziska , Klenk Jochen , Clemson Lindy , Todd Chris , Dams Judith , König Hans-Helmut , Becker Clemens , Schwenk Michael
Published: January 2023

Background

the individually delivered Lifestyle-integrated Functional Exercise (LiFE) was shown to improve physical activity (PA) and reduce fall incidence, however being rather resource-consuming due to one-to-one delivery. A potentially less resource-intensive group format (gLiFE) was developed and compared against the original program, considering higher risk of falling due to possible PA enhancement.

Objective

to investigate non-inferiority in terms of PA-adjusted fall risk and cost-effectiveness of gLiFE at 12-month follow-up.

Design

single-blinded, randomised, multi-centre non-inferiority trial.

Setting

community.

Subjects

in total, 309 adults aged 70+ years at risk of or with history of falling; n = 153 in gLiFE, n = 156 in LiFE.

Methods

LiFE was delivered one-to-one at the participants’ homes, gLiFE in a group. PA-adjusted fall risk was analysed using negative binomial regression to compare incidence rate ratios (IRR). Cost-effectiveness was presented by incremental cost-effectiveness ratios and cost-effectiveness acceptability curves, considering quality-adjusted life years, PA and falls as effect measures. Secondary analyses included PA (steps/day) and fall outcomes.

Results

non-inferiority was inconclusive (IRR 0.96; 95% confidence interval, CI 0.67; 1.37); intervention costs were lower for gLiFE, but cost-effectiveness was uncertain. gLiFE participants significantly increased PA (+1,090 steps/day; 95% CI 345 and 1.835) versus insignificant increase in LiFE (+569, 95% CI −31; 1,168). Number of falls and fallers were reduced in both formats.

Conclusion

non-inferiority of gLiFE compared with LiFE was inconclusive after 12 months. Increases in PA were clinically relevant in both groups, although nearly twice as high in gLiFE. Despite lower intervention costs of gLiFE, it was not clearly superior in terms of cost-effectiveness.
Examining the effect of interventions in emergency care for older people using a system dynamics decision support tool
Authors: England Tracey , Brailsford Sally , Evenden Dave , Street Andrew , Maynou Laia , Mason Suzanne M , Preston Louise , Burton Christopher , Van Oppen James , Conroy Simon
Published: January 2023

Background

Rising demand for Emergency and Urgent Care is a major international issue and outcomes for older people remain sub-optimal. Embarking upon large-scale service development is costly in terms of time, energy and resources with no guarantee of improved outcomes; computer simulation modelling offers an alternative, low risk and lower cost approach to explore possible interventions.

Method

A system dynamics computer simulation model was developed as a decision support tool for service planners. The model represents patient flow through the emergency care process from the point of calling for help through ED attendance, possible admission, and discharge or death. The model was validated against five different evidence-based interventions (geriatric emergency medicine, front door frailty, hospital at home, proactive care and acute frailty units) on patient outcomes such as hospital-related mortality, readmission and length of stay.

Results

The model output estimations are consistent with empirical evidence. Each intervention has different levels of effect on patient outcomes. Most of the interventions show potential reductions in hospital admissions, readmissions and hospital-related deaths.

Conclusions

System dynamics modelling can be used to support decisions on which emergency care interventions to implement to improve outcomes for older people.
multiMiAT: an optimal microbiome-based association test for multicategory phenotypes
Authors: Sun Han , Wang Yue , Xiao Zhen , Huang Xiaoyun , Wang Haodong , He Tingting , Jiang Xingpeng
Published: January 2023

Microbes can affect the metabolism and immunity of human body incessantly, and the dysbiosis of human microbiome drives not only the occurrence but also the progression of disease (i.e. multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, the existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g. disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test for multicategory phenotypes (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the success of our method. Furthermore, multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer as well as for diverse statuses of Clostridium difficile infections.
SPNE: sample-perturbed network entropy for revealing critical states of complex biological systems
Authors: Zhong Jiayuan , Ding Dandan , Liu Juntan , Liu Rui , Chen Pei
Published: January 2023

Complex biological systems do not always develop smoothly but occasionally undergo a sharp transition; i.e. there exists a critical transition or tipping point at which a drastic qualitative shift occurs. Hunting for such a critical transition is important to prevent or delay the occurrence of catastrophic consequences, such as disease deterioration. However, the identification of the critical state for complex biological systems is still a challenging problem when using high-dimensional small sample data, especially where only a certain sample is available, which often leads to the failure of most traditional statistical approaches. In this study, a novel quantitative method, sample-perturbed network entropy (SPNE), is developed based on the sample-perturbed directed network to reveal the critical state of complex biological systems at the single-sample level. Specifically, the SPNE approach effectively quantifies the perturbation effect caused by a specific sample on the directed network in terms of network entropy and thus captures the criticality of biological systems. This model-free method was applied to both bulk and single-cell expression data. Our approach was validated by successfully detecting the early warning signals of the critical states for six real datasets, including four tumor datasets from The Cancer Genome Atlas (TCGA) and two single-cell datasets of cell differentiation. In addition, the functional analyses of signaling biomarkers demonstrated the effectiveness of the analytical and computational results.
Residential turnover and crime—Evidence from administrative data for England and Wales
Authors: Braakmann Nils
Published: January 2023

This article combines administrative data on housing transactions with monthly crime data for the years 2014–18 to investigate the link between residential turnover and crime. Using a panel of 34,753 small neighbourhoods in England and Wales as well as street-level data for London, estimates from models with multiple fixed effects suggest that higher turnover is associated with higher overall crime rates. These effects are small and driven by increases in property and violent crime. Using information on price growth, I document differential effects for high-turnover, high price growth (‘attractive’) and high turnover, low price growth (‘declining’) areas.
Long-term clinical trials of biologics in plaque psoriasis demonstrate heterogeneous study designs
Authors: Grolleau Chloé , Le Cleach Laurence , Shourick Jason , Sbidian Emilie , Afach Sivem
Published: January 2023

Numerous network meta-analyses have provided comparative efficacy and safety data for treatments in psoriaasis over a short period (8-24 weeks). So, we conducted a systematic review to map the design and synthesize all 1-year efficacy and safety data of biologic treatments for moderate-to-severe psoriasis from the randomized controlled trials (RCTs) included in the Cochrane review (Sbidian et al., 2022).

Among the 81 RCTs included, many different designs are presented after the induction phase. Within a single trial, each arm (placebo, intervention, active comparator) could have a different design: single randomization; crossover; re-randomization. In addition, there was selection of patients into each arm based on the level of PASI response achieved or PGA achieved.
A milestone reached in the standardization of lichen sclerosus trial outcomes
Authors: Thorlacius Linnea , Alam Murad
Published: January 2023

CORALS (Core Outcomes for Research in Lichen Sclerosus) reached an important milestone with their final consensus on three quite broad core domains: clinical signs, symptoms and LS specific quality of life.

This commentary illuminates why there is need for more methodological guidance in core outcome set development processes regarding: (1) the appropriate level of granularity during the domain definition process; and (2) the preferred number of final core domains.
The pursuit of equity in skin cancer prevention: a survey-based investigation of total body skin exam awareness and utilization across Fitzpatrick skin type
Authors: Han Joseph , Baek Peter , Da Rosa Joel Correa , Young Jade N , Poplausky Dina , Tai Hansen , Owji Shayan , Ungar Benjamin , Gulati Nicholas , Ungar Jonathan
Published: January 2023

Disparities in early detection of skin cancer are reflected in the disproportionate melanoma-associated mortality among people with skin of colour. To better characterize the drivers of this disparity, we sought to investigate differences in skin cancer surveillance by total body skin examination stratified by Fitzpatrick skin type through a patient survey during focused dermatology clinic visits at a tertiary academic institution.
Direct brain recordings suggest a causal subsequent-memory effect
Authors: Rubinstein Daniel Y , Weidemann Christoph T , Sperling Michael R , Kahana Michael J
Published: January 2023

Endogenous variation in brain state and stimulus-specific evoked activity can both contribute to successful encoding. Previous studies, however, have not clearly distinguished among these components. We address this question by analysing intracranial EEG recorded from epilepsy patients as they studied and subsequently recalled lists of words. We first trained classifiers to predict recall of either single items or entire lists and found that both classifiers exhibited similar performance. We found that list-level classifier output—a biomarker of successful encoding—tracked item presentation and recall events, despite having no information about the trial structure. Across widespread brain regions, decreased low- and increased high-frequency activity (HFA) marked successful encoding of both items and lists. We found regional differences in the hippocampus and prefrontal cortex, where in the hippocampus HFA correlated more strongly with item recall, whereas, in the prefrontal cortex, HFA correlated more strongly with list performance. Despite subtle differences in item- and list-level features, the similarity in overall classification performance, spectral signatures of successful recall and fluctuations of spectral activity across the encoding period argue for a shared endogenous process that causally impacts the brain’s ability to learn new information.
Consensus recommendations for COVID-19-related myocarditis in athletes: proof of concept—case report
Authors: Abdelfattah Omar M , Mathur Tarun , Martinez Matthew W
Published: January 2023

Background

Post-viral myocarditis has been associated with sudden cardiac death in athletes. Since the beginning of the COVID-19 pandemic, the concern of post-viral myocarditis impacting the professional athletic community has been present.

Case summary

An elite-level basketball player presented after a positive COVID-19 test with findings consistent with ventricular tachycardia related to myocardial fibrosis/scar from a COVID-19-related myocarditis. Although rare, COVID-19 myocarditis can occur. This case illustrates how the consensus guidelines for return-to-play correctly identified the player as high risk with appropriate downstream evaluation by cardiac magnetic resonance (CMR) imaging. The stepwise approach is illustrated in this case and highlights the utility and success of the algorithm when approaching athletes with COVID-19-related myocarditis risk and determining a return to exercise.

Discussion

Diligence is required to identify competitive athletes with features suggestive of myocarditis at the initial presentation and with the return to exercise. Cardiopulmonary symptoms in the setting of recent COVID-19 infection should prompt additional testing in a stepwise fashion and often benefit from CMR in addition to the triad testing with electrocardiography, echocardiography, and cardiac troponin measurement to further investigate clinical presentations of COVID-19-related myocarditis.
Benedicamus Domino: delight in singing praise to God at Las Huelgas of Burgos
Authors: Catalunya David
Published: January 2023

The Las Huelgas Codex (Hu) features one of the most varied collections of medieval polyphony in Europe. It contains the repertory of Mass Ordinary settings, sequences, organa, conductus and motets that was in use at the royal nunnery of Las Huelgas in Burgos during the 13th and 14th centuries. While most of this repertory is known from other earlier sources, several of the numerous settings of the Benedicamus Domino in Hu are unique pieces that reflect an apparently local practice. Closer inspection reveals, however, that nearly all of these ‘unique’ Benedicamus settings were created by borrowing and reworking musical material from other sections of the manuscript. This article considers the Benedicamus Domino settings as a musically cohesive sub-repertory in Hu, showcasing a rich array of reworking techniques. The article also considers the ritual function of the Benedicamus Domino within the liturgy of the royal convent, as well as the performance context and the distribution of singing duties between the nuns and the clerics of the monastery.
Results from rapid-cycle recurrent genomic selection in spring bread wheat
Authors: Dreisigacker Susanne , Pérez-Rodríguez Paulino , Crespo-Herrera Leonardo , Bentley Alison R , Crossa José
Published: January 2023

Genomic selection (GS) in wheat breeding programs is of great interest for predicting the genotypic values of individuals, where both additive and nonadditive effects determine the final breeding value of lines. While several simulation studies have shown the efficiency of rapid-cycling GS strategies for parental selection or population improvement, their practical implementations are still lacking in wheat and other crops. In this study, we demonstrate the potential of rapid-cycle recurrent GS (RCRGS) to increase genetic gain for grain yield (GY) in wheat. Our results showed a consistent realized genetic gain for GY after 3 cycles of recombination (C1, C2, and C3) of bi-parental F1s, when summarized across 2 years of phenotyping. For both evaluation years combined, genetic gain through RCRGS reached 12.3% from cycle C0 to C3 and realized gain was 0.28 ton ha−1 per cycle with a GY from C0 (6.88 ton ha−1) to C3 (7.73 ton ha−1). RCRGS was also associated with some changes in important agronomic traits that were measured (days to heading, days to maturity, and plant height) but not selected for. To account for these changes, we recommend implementing GS together with multi-trait prediction models.
ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS
Authors: dos Anjos Gabriele Alves , Gomes Cintia Pavao , Oliveira Diego Brandão , Maia Julia de Carvalho , Dalfovo Milena Prigol , Carvalho Gabriela Domingues , Falcon Bruna Thaytala Quintino
Published: January 2023

BACKGROUND

Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself.

AIMS

This systematic review and meta-analysis aimed to assess the incidence of extraintestinal manifestations in patients receiving Vedolizumab and to investigate whether these adverse events are indeed drug-related.

METHODS

Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of articular events in patients with Crohn’s Disease or Ulcerative Colitis who were treated with Vedolizumab. The considered outcomes were new-onset or worsening of pre-existing joint manifestations. We used Revman to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI).

RESULTS

The search strategy yielded 4.206 articles. After removal of duplicates and screening of results, 4 randomized studies met the inclusion criteria (Figure 1).

A total of 2.466 patients with moderately to severe IBD were included. Of those, 1822 were randomized to intervention group, with Vedolizumab administration, and 644 to placebo. In the intervention group, 232 patients developed arthritis or arthralgia of any kind, versus 66 patients of placebo group (95% CI 0.7%-1.3%; Figure 2). Of those patients, 73,8% and 33% had prior treatment with anti-TNF and immunomodulators, respectively. 63% and 15% also had prior anti-TNF and immunomodulators previous failure, respectively.

CONCLUSION

The meta-analysis presented above shows a result without statistical significance to say that vedolizumab is responsible for the manifestations previously described. Therefore, it is necessary to hypothesize that the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, the body's response to the drugs or the exclusion of corticosteroids or anti-TNF from concomitant treatment with Vedolizumab. More studies with larger samples are needed, especially randomized clinical trials comparing Anti-TNF, corticosteroids and immunomodulators to assess the incidence of joint manifestations and even other rheumatologic manifestations in patients with Inflammatory Bowel Disease.
A PRECLINICAL MODEL OF STENOTIC CROHN’S DISEASE FOR THE STUDY OF MECHANISMS OF MOTILITY DYSFUNCTION IN IBD
Authors: Johnson John , Geesala Ramasatyaveni , Zhang Ke , Shi Xuan-Zheng
Published: January 2023

BACKGROUND AND AIMS

Motility dysfunction is present in patients with stenotic Crohn’s disease (CD) and contributes to cramps, diarrhea and constipation. However, mechanisms for motility dysfunction in CD are incompletely understood. Mechanical stress, i.e. inflammatory infiltration, edema, stenosis, and distention, is commonly encountered in CD. We tested the hypothesis in a rat model of stenotic CD that mechanical stress-induced expression of mechano-sensitive genes such as cyclo-oxygenase-2 (COX-2) may account for motility dysfunction in the inflammation site and the mechanically distended site prior to inflammation.

ANIMAL MODEL AND METHODS

Rat model of CD-like colitis was induced by intracolonic instillation of TNBS 65 mg/kg in 250 µL of 40% ethanol. Control rats were treated with intracolonic saline instillation. When rats were fed with regular pellet food, instillation of TNBS led to localized transmural inflammation with stenosis in the instillation site (site I) and lumen distention in the colon segment proximal to inflammation (site P). However, when rats were fed exclusively with liquid diet, inflammation-associated stenosis and mechanical distention was eliminated. Rats were euthanized by 7 days.

RESULTS

1) Compared to controls, COX-2 mRNA expression was increased by 13.1(± 2.5)-fold in site I and 16.6(±4.3)-fold in the mechanically distended site P, but not in the non-distended site D. This data indicates a mechanosensitive mechanism in COX-2 expression. If mechanical distention in CD was prevented by feeding rats exclusively with clear liquid diet, the increase of COX-2 mRNA expression was attenuated in sites I and P. Further investigation showed that increased expression of COX-2 occurs mainly in the colonic smooth muscle cells (SMC) of the distended colon. 2) We found that COX-2 expression was robustly induced by mechanical stretch (18% static stretch) in vitro in rat colonic smooth muscle cells (SMC). 3) Inflammation led to significant suppression of colon circular muscle contractility not only in site I but also in distended site P of CD-like rats. Muscle contractility in site D was not significantly affected by inflammation. Moreover, clear liquid diet treatment significantly improved muscle contractility in sites P and I. 4) To determine the role of COX-2 in smooth muscle dysfunction in the CD model, COX-2 inhibitor NS-398 (5 mg/kg, i.p. daily) was administered in control and CD rats. We found that NS-398 significantly improved muscle contractility in CD rats in sites P and I.

CONCLUSIONS

Our study found that up-regulation of COX-2 expression in stenotic CD-like colitis is dependent on mechanical stress. COX-2 inhibitor improved colon smooth muscle contractility in colitis. Thus, mechanosensitive expression of COX-2 may play a critical role in smooth muscle dysfunction and dysmotility in CD.
LMT503, A NOVEL THERAPY FOR INFLAMMATORY BOWEL DISEASE THROUGH MACROPHAGE POLARIZATIONS BY METABOLIC REPROGRAMMING OF ACTIVATED MACROPHAGE
Authors: Lee Wheeseong , Chung Hyo Kyun , Kim Jusik , Ko Inseok , Yang Chul-Su , Kim Hyo Keun
Published: January 2023

Macrophages are the first line of defense against self-stimuli and non-self-pathogens and adopt diverse activation states by reprogramming their cell metabolism and thereby polarizing their phenotypes in order to drive their pro-inflammatory or pro-resolving responses. As the key gatekeeper of intestinal immune homeostasis, macrophage polarization has an important effect on maintaining tissue homeostasis with inducing resolution, and therefore macrophages phenotype alteration by modulating their cellular metabolism might be a novel therapeutic approach in IBD.

LMT503 is an orally available organic small molecule and exerted the macrophage polarization from M1-like inflammatory macrophage to M2-like anti-inflammatory macrophages in LPS-induced bone marrow-derived macrophage in vitro experiment. The expression level of M1-related intracellular functional marker iNOS was suppressed by LMT503, while Arg-1 which is M2-associated marker was increased. LMT503 also performed metabolic reprogramming with decreasing anabolic metabolism but enhancing catabolic metabolism including mitochondrial metabolism.

In the therapeutic settings using various IBD in vivo models such as DSS-induced acute/chronic mice models and adoptive T cell transfer mice model, LMT503 exerted macrophage polarization with showing reduced expression level of M1 markers such as iNOS, CD80, and CD86 but increased expression of M2 markers like Arg-1, CD168, and CD206. LMT503 mitigated inflammation with decreased production of inflammatory cytokines (TNF-a, IL-6, IL-1b, IL-18), increased anti-inflammatory cytokines (IL-10, IL-22), and reduced neutrophil infiltrations. In the addition to increased ratio of M2/M1 macrophages, LMT503 increased ratio of Treg/Th17.

LMT503 also induced epithelial restitution with increased number of goblet cells, and showed decreased bacterial translocation from gut to mesenteric lymph node.

In a chronic IBD mice model, LMT503 showed reduced intestinal fibrotic marker a-SMA which is one of critical complications for patients with long-term IBD.

Mode of action through macrophage polarization was proved by using a macrophage-depleted IBD in vivo model, and LMT503 did not improve the disease associate index or inflammation. Also LMT503 showed re-storing immunity in an in vivo study of challenging pathogen to LMT503-treated and washed-out model, which avoids the possibility of an opportunistic infections.

In summary, LMT503 was very efficacious in various IBD in vivo models with showing the resolution of intestinal inflammation and mucosal healing through improved epithelial restitution via macrophage polarizations, and this approach can be a very effective and safe therapy for multifaceted IBD. The first in human study with LMT503 will be initiating in 4Q 2022.
ACCELERATED INFLIXIMAB INFUSION SAFETY AND TOLERABILITY IS NON-INFERIOR TO STANDARD INFUSION PROTOCOL IN INFLAMMATORY BOWEL DISEASE PATIENTS – A RANDOMIZED CONTROLLED STUDY
Authors: Abushamma Suha , Walker Ted , Garza Kevin , Chen Chien-Huan
Published: January 2023

BACKGROUND & AIM

Infliximab is typically given over a standard infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. Several retrospective and prospective studies have assessed the safety of accelerated infliximab infusions, but not in a randomized controlled setting. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared to the standard 2 hour infusion.

METHODS

This open label randomized trial was done at a tertiary IBD center in the United States. Patients with an established diagnosis of IBD receiving maintenance infliximab infusions at one of our centers were eligible for inclusion. We excluded patients with a history of infusion reactions and those with known antidrug antibodies to infliximab. Patients were randomly assigned (1:1) to the 1 hour infusion (study) and 2 hour infusion (control) groups using an independent computerized randomization system. The primary outcome was to assess the rate of infusion reactions in the standard 2 hour compared to the accelerated 1 hour study groups. Secondary outcomes were assessment of the effect of pre-medications and concomitant immunomodulators on the rate of infusion reactions, and cost effectiveness analysis. Sample size calculation was based on an infusion reaction rate of 3%, as suggested by recent studies. In order to show a non-inferiority of the accelerated infusion time assuming an infusion reaction rate of 3% while allowing for a 4% non-inferiority limit, a total of 538 infusions would be needed. This would provide a power of 80% and significant alpha of 0.05. Non-inferiority was assessed using Farrington-Manning score test. This trial is registered with ClinicalTrials.gov, NCT05340764.

RESULTS

From November 2020 to November 2021, we assessed the eligibility of 448 patients, of whom 352 (78%) were excluded primarily due to infusions being received at an outside institution, or patient refusal. Thus, 96 (22%) patients were randomly assigned: 51 (53%) to the 1 hour infusion study group and 45 (47%) to the 2 hour infusion control group. Over a median time of 1 year, a total of 685 infusions were administered: 309 infusions in the control group, and 376 in the study group. 57 (18%) of 309 infusions in the control group and 45 (12%) of 376 infusions in the study group experienced an infusion reaction. The only infusion reaction experienced was hypotension, all of which were asymptomatic and none required infusion discontinuation. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18 – 3.52], p=0.01). Average costs were estimated to reduce by 37% in the accelerated infusion group.

CONCLUSION

Accelerated 1 hour infliximab infusions are non-inferior in safety and superior in cost-effectiveness compared to standard 2 hour infusions in IBD patients.
CURCUMIN-QINGDAI COMBINATION FOR PATIENTS WITH ACTIVE ULCERATIVE COLITIS: A RANDOMIZED DOUBLE-BLINDED PLACEBO-CONTROLLED CLINICAL TRIAL
Authors: Ben-Horin Shomron , Salomon Nir , Karampekos Georgios , Viazis Nikos , Lahat Adi , Ungar Bella , Eliakim Rami , Kriger-Sharabi Ofra , Reiss-Mintz Hilla , Yanai Henit , Dotan Iris , Zittan Eran , Hirsch Ayal , Maharshak Nitsan , Mantzaris Gerassimos , Kopylov Uri
Published: January 2023

BACKGROUND

The herbal extracts Curcumin and QingDai were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC.

METHODS

This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either Curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS.

RESULTS

59 patients were enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized. The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p<0.001), 50% calprotectin-reduction in 46.4% versus 15.4% (p=0.08) and endoscopic improvement in 75% versus 20% (p=0.036), in the CurQD and placebo groups, respectively. The overall rate of adverse events was comparable between the groups. Among week-8 responders to CurQD, additional 8 weeks of treatment with curcumin alone resulted in 93%, 80% and 40% with maintained clinical response, clinical remission and clinic-biomarker response, respectively, at week 16. CurQD treatment uniquely resulted in activation of the AhR pathway, as gauged by up-regulated expression of CYP1A1 in the rectal mucosa, which was not observed among patients receiving placebo, nor was it observed in patients responding to 5ASA or biologic drugs.

CONCLUSION

In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC.