bluuebunny/crossref_metadata_2025 huggingface dataset:
Online revenue maximization for server pricing
Authors: Boodaghians Shant , Fusco Federico , Leonardi Stefano , Mansour Yishay , Mehta Ruta
Published: January 2022

Efficient and truthful mechanisms to price resources on servers/machines have been the subject of much work in recent years due to the importance of the cloud market. This paper considers revenue maximization in the online stochastic setting with non-preemptive jobs and a unit capacity server. One agent/job arrives at every time step, with parameters drawn from the underlying distribution. We design a posted-price mechanism which can be efficiently computed and is revenue-optimal in expectation and in retrospect, up to additive error. The prices are posted prior to learning the agent’s type, and the computed pricing scheme is deterministic, depending only on the length of the allotted time interval and on the earliest time the server is available. We also prove that the proposed pricing strategy is robust to imprecise knowledge of the job distribution and that a distribution learned from polynomially many samples is sufficient to obtain a near-optimal truthful pricing strategy.
Fragments from the Ājīvikas
Authors: Balcerowicz Piotr
Published: January 2022

The paper examines available references to the Ājīvikas that are often identified by scholars, notably by Basham (1951), as genuine quotations from Ājīvikas’ lost works. In addition, the paper analyses some additional material not previously indentifed as possible quotations relevant to Ājīvikism. Unfortunately, none of such references seem to be genuinely derived from an Ājīvika source: All of such passages or verses previously considered genuinely taken from Ājīvika literature turn out to have been composed by non-Ājīvika authors and usually derive either from Jaina works or from fables and narrative literature. There is no clear proof that the Ājīvikas developed their own Sanskrit literature (in addition to Prakrit works), much less philosophical literature in Sanskrit. Further, the faithfulness and reliability of reports of the Ājīvikas and paraphrases of their views cannot be assessed with any certainty.
Mental Health in Multiple Sclerosis During the COVID-19 Outbreak: A Delicate Balance between Fear of Contagion and Resilience
Authors: Rosa Laura , Scandurra Cristiano , Chiodi Alessandro , Petracca Maria , Costabile Teresa , Lauro Francesca , Moccia Marcello , Carotenuto Antonio , Maldonato Nelson Mauro , Brescia Morra Vincenzo , Lanzillo Roberta
Published: January 2022

The current study aimed at exploring the relationship between objective disability, illness perceptions, resilience, fear of COVID-19, and psychological distress (i.e., anxiety, depression, and stress) in people with multiple sclerosis (pwMS) during the second wave of the COVID-19 outbreak. A group of 122 pwMS recruited in an Italian university hospital took part in this cross-sectional monocentric study. Hierarchical multiple linear regression analyses were performed to assess the strength of the hypothesized associations. Results indicated that, differently from cognitive impairment, motor disability was positively associated with anxiety. However, accounting for subjective illness perception, such association was no longer significant. Moreover, accounting for both protective and risk factors in the models, even illness perception was no longer significant, highlighting the central role of resilience and fear of COVID-19 in explaining the negative emotional outcomes. Implications for clinical interventions and psychoeducational trainings are discussed.
What a Home Does
Authors: Jenkins David , Brownlee Kimberley
Published: January 2022

Analytic philosophy has largely neglected the topic of homelessness. The few notable exceptions, including work by Jeremy Waldron and Christopher Essert, focus on our interests in shelter, housing, and property rights, but ignore the key social functions that a home performs as a place in which we are welcomed, accepted, and respected. This paper identifies a ladder of home-related concepts which begins with the minimal notion of temporary shelter, then moves to persistent shelter and housing, and finally to the rich notion of a home which focuses on meeting our social needs including, specifically, our needs to belong and to have meaningful control over our social environment. This concept-ladder enables us to distinguish the shelterless from the sheltered; the unhoused from the housed; and the unhomed from the homed. It also enables us to decouple the concept of a home from property rights, which reveals potential complications in people’s living arrangements. For instance, a person could be sheltered but unhoused, housed but homeless, or, indeed, unhoused but homed. We show that we should reserve the concept of home to capture the rich idea of a place of belonging in which our core social needs are met.
Money for Nothing: The Impact of Compensation on Customers’ Bad-Mouthing in Service Recovery Encounters
Authors: Arsenovic Jasenko , Edvardsson Bo , Otterbring Tobias , Tronvoll Bård
Published: January 2022

As one of the retailer’s most potent recovery tactics to offset disgruntled customers, firms invest heavily in compensation to increase customer satisfaction and improve loyalty. However, the effectiveness of this tactic remains unclear. This study examines whether firm-offered compensation affects customers’ emotional responses and bad-mouthing behavior (i.e., telling others about a particular problem). Importantly, the study investigates whether the level of collaboration during the recovery encounter moderates the link between compensation and customers’ emotional responses, and whether collaborative efforts influence the effectiveness of compensation. The findings indicate that collaboration during the recovery encounter is necessary if compensation is to mitigate negative emotional responses, with downstream effects on bad-mouthing behavior. In confirming the importance of collaboration during recovery encounters, the findings have critical managerial and financial implications.
Geospatial model of COVID-19 spreading and vaccination with event Gillespie algorithm
Authors: Temerev Alexander , Rozanova Liudmila , Keiser Olivia , Estill Janne
Published: January 2022

We have developed a mathematical model and stochastic numerical simulation for the transmission of COVID-19 and other similar infectious diseases that accounts for the geographic distribution of population density, detailed down to the level of location of individuals, and age-structured contact rates. Our analytical framework includes a surrogate model optimization process to rapidly fit the parameters of the model to the observed epidemic curves for cases, hospitalizations, and deaths. This toolkit (the model, the simulation code, and the optimizer) is a useful tool for policy makers and epidemic response teams, who can use it to forecast epidemic development scenarios in local settings (at the scale of cities to large countries) and design optimal response strategies. The simulation code also enables spatial visualization, where detailed views of epidemic scenarios are displayed directly on maps of population density. The model and simulation also include the vaccination process, which can be tailored to different levels of efficiency and efficacy of different vaccines. We used the developed framework to generate predictions for the spread of COVID-19 in the canton of Geneva, Switzerland, and validated them by comparing the calculated number of cases and recoveries with data from local seroprevalence studies.
COVID-19: Impact on the HIV and Tuberculosis Response, Service Delivery, and Research in South Africa
Authors: Abdool Karim Quarraisha , Baxter Cheryl
Published: January 2022

Purpose of Review

To describe how mitigation measures against COVID-19 have impacted HIV and TB research in South Africa.

Recent Findings

South Africa has the highest number of COVID-19 (34%) cases in Africa, accounting for 43% of all reported COVID-19-related deaths on the continent. The country accounts for 20% of all people living with HIV and ranked third in the world for new TB infections in 2019.

While South Africa’s investments in its HIV and TB responses enabled it to pivot rapidly to respond to the emerging COVID-19 epidemic, it negatively impacted the HIV and TB response through temporary suspension of research, diversion of key resources for HIV and TB control, and patient access to health care facilities; the full extent of this has yet to emerge. Success in integrating responses to the colliding epidemics could potentially enhance survival outcomes and ensure gains made to date in HIV and TB are not reversed and we stay on track toward achieving the UN 2030 Sustainable Development Goals.
Exploring mindful consumption, ego involvement, and social norms influencing second-hand clothing purchase
Authors: Zahid Nawaz Muhammad , Khan Jashim , Tao Meng
Published: January 2022

Second-hand clothing (SHC) benefits society by reducing the wastage of natural resources. Research in the purchase of second-hand clothing is a debated topic. It is not yet clear whether caring for self, community, and nature drives the purchase of second-hand clothing. This study unpacks the intervening factors that drive second-hand clothing purchases underpinning attitude-intention and self-determination theories. The primary purpose is to examine the direct relationship between a) mindful consumption, b) ego-involvement, c) social norms on second-hand clothing purchase intention of young consumers. The mediation of ego-involvement and social norm is examined on the above relationship. A total of 314 usable questionnaires following the convenience and purposive snowball sampling techniques were gathered from China. The structural equation model (SEM) two-step approach analyzed the data. SmartPLS3 statistical package used to run the measurement and structural model analyses. IPMA analysis confirms mindful consumption as an important factor; hence ego-involvement drives the performance of the stated relationship. Ego-involvement mediates the relationship between mindful consumption and second-hand clothing purchase. This study bridges the unanswered questions and highlights the importance of mindful consumption, an essential driver of consumer behavior. Managers are encouraged to promote mindful consumption values in marketing communication to drive sustainability.
Bovine Serum Albumin Detection by Graphene Oxide Coated Long-Period Fiber Grating
Authors: Wang Ruiduo , Wu Hao , Qi Mei , Han Jing , Ren Zhaoyu
Published: January 2022

A biosensor for bovine serum albumin (BSA) detection by graphene oxide (GO) functionalized micro-taped long-period fiber grating (GMLPG) was demonstrated. The amide bond connected between the GO and BSA enabled the BSA to attach onto the fiber surface, which changed the effective refractive index of the cladding mode and characterized the concentration of the BSA. This real-time monitoring system demonstrated a sensing sensitivity of 1.263 nm/(mg/mL) and a detection limit of 0.043 mg/mL. Moreover, it illustrated superior measurement performance of higher sensitivity in the presence of glucose and urea as the interference, which showed static sensitivities of ∼1.476 nm/(mg/mL) and 1.504 nm/(mg/mL), respectively. The proposed GMLPG demonstrated a great potential for being employed as a sensor for biomedical and biochemical applications.
The effect of pH, temperature, and inoculum on the fermentation of pulp and paper biosludge: increasing the nutrient availability for rearing of black soldier fly larvae
Authors: Niero Luisa , Norgren Robert , Kumpiene Jurate , Jonsson Anders
Published: January 2022

Pulp and paper production is one of the largest global industries producing annually 400 million metric tons of pulp and paper products and 6 million tons of pulp and paper biosludge (PPBS). From a resource efficiency and sustainability perspective, there is a need for improving PPBS management. This study assessed fermentation of PPBS as pretreatment to improve PPBS feasibility as feed for black soldier fly larvae. The impact of temperature, pH, and inoculum on the concentration of soluble chemical oxygen demand (sCOD) and volatile fatty acids (VFA) was assessed. An initial pH of 10 and the addition of inoculum from an anaerobic digester substantially increased the concentration of sCOD. The obtained concentration of VFA was low compared to the VFA concentration needed to improve the growth of Black Soldier Fly Larvae (BSFL). The PPBS is recalcitrant to fermentation because of the high content of lignocellulose. Fermentation as done in this study does not convert PPBS to a feasible feed for black soldier fly larvae; thus, further research on improved fermentation is needed. However, fermentation at alkaline pH and addition of inoculum do increase the final pH of PPBS which improves its feasibility as feed for BSFL. Future studies should explore pH > 10 and temperatures > 55 °C to increase sCOD and improving generation of VFA by removal of inhibiting substances, testing other types of inoculum (rumen microorganisms) and co-fermentation.
Arctic Sea Ice Type Classification by Combining CFOSCAT and AMSR‐2 Data
Authors: Xu Rui , Zhao Chaofang , Zhai Xiaochun , Chen Ge
Published: January 2022

First‐year ice (FYI) and multi‐year ice (MYI) are the two most common ice types in the Arctic. In this article, the classification of FYI and MYI over the Arctic region in the winter of 2019/2020 and 2020/2021 is investigated by combining the data of the scatterometer on Chinese‐French Oceanography Satellite (CFOSCAT) and the Advanced Microwave Scanning Radiometer‐2 (AMSR‐2) based on the Tree Augmented Naive Bayes (TAN) classifier. The CFOSCAT/AMSR ice type classification results are validated by using Ocean and Sea Ice Satellite Application Facility (OSI SAF) sea ice type products, Canadian Ice Service ice charts, and synthetic‐aperture radar data. The results showed that the overall MYI extent change trend retrieved from CFOSCAT/AMSR was consistent with the OSI SAF product with a correlation coefficient of 0.89 for winter of 2019/2020 and 0.88 for 2020/2021. In addition, CFOSCAT/AMSR identified a slightly larger MYI extent than OSI SAF and the average deviation between them is 10.1% for 2019/2020 while 8.3% for 2020/2021. Besides, CFOSCAT/AMSR can identify more MYI pixels when the MYI concentration is relatively low in the Western Arctic region. We also used CFOSCAT data only to retrieve ice type and found that the active and passive microwave data fusion could capture more MYI pixels located near the boundary of MYI and FYI main body, and the introduction of AMSR‐2 data in ice type classification could reduce the error caused by the abnormal values of CFOSCAT parameters.
Parsimonious Velocity Inversion Applied to the Los Angeles Basin, CA
Authors: Muir Jack B. , Clayton Robert W. , Tsai Victor C. , Brissaud Quentin
Published: January 2022

The proliferation of dense arrays promises to improve our ability to image geological structures at the scales necessary for accurate assessment of seismic hazard. However, combining the resulting local high‐resolution tomography with existing regional models presents an ongoing challenge. We developed a framework based on the level‐set method that infers where local data provide meaningful constraints beyond those found in regional models ‐ for example the Community Velocity Models (CVMs) of southern California. This technique defines a volume within which updates are made to a reference CVM, with the boundary of the volume being part of the inversion rather than explicitly defined. By penalizing the complexity of the boundary, a minimal update that sufficiently explains the data is achieved. To test this framework, we use data from the Community Seismic Network, a dense permanent urban deployment. We inverted Love wave dispersion and amplification data, from the Mw 6.4 and 7.1 2019 Ridgecrest earthquakes. We invert for an update to CVM‐S4.26 using the Tikhonov Ensemble Sampling scheme, a highly efficient derivative‐free approximate Bayesian method. We find the data are best explained by a deepening of the Los Angeles Basin with its deepest part south of downtown Los Angeles, along with a steeper northeastern basin wall. This result offers new progress toward the parsimonious incorporation of detailed local basin models within regional reference models utilizing an objective framework and highlights the importance of accurate basin models when accounting for the amplification of surface waves in the high‐rise building response band.
Global Atmospheric OCS Trend Analysis From 22 NDACC Stations
Authors: Hannigan James W. , Ortega Ivan , Shams Shima Bahramvash , Blumenstock Thomas , Campbell John Elliott , Conway Stephanie , Flood Victoria , Garcia Omaira , Griffith David , Grutter Michel , Hase Frank , Jeseck Pascal , Jones Nicholas , Mahieu Emmanuel , Makarova Maria , De Mazière Martine , Morino Isamu , Murata Isao , Nagahama Toomo , Nakijima Hideaki , Notholt Justus , Palm Mathias , Poberovskii Anatoliy , Rettinger Markus , Robinson John , Röhling Amelie N. , Schneider Matthias , Servais Christian , Smale Dan , Stremme Wolfgang , Strong Kimberly , Sussmann Ralf , Te Yao , Vigouroux Corinne , Wizenberg Tyler
Published: January 2022

Carbonyl sulfide (OCS) is a non‐hygroscopic trace species in the free troposphere and a large sulfur reservoir maintained by both direct oceanic, geologic, biogenic, and anthropogenic emissions and the oxidation of other sulfur‐containing source species. It is the largest source of sulfur transported to the stratosphere during volcanically quiescent periods. Data from 22 ground‐based globally dispersed stations are used to derive trends in total and partial column OCS. Middle infrared spectral data are recorded by solar‐viewing Fourier transform interferometers that are operated as part of the Network for the Detection of Atmospheric Composition Change between 1986 and 2020. Vertical information in the retrieved profiles provides analysis of discreet altitudinal regions. Trends are found to have well‐defined inflection points. In two linear trend time periods ∼2002 to 2008 and ∼2008 to 2016 tropospheric trends range from ∼0.0 to (1.55 ± 0.30%/yr) in contrast to the prior period where all tropospheric trends are negative. Regression analyses show strongest correlation in the free troposphere with anthropogenic emissions. Stratospheric trends in the period ∼2008 to 2016 are positive up to (1.93 ± 0.26%/yr) except notably low latitude stations that have negative stratospheric trends. Since ∼2016, all stations show a free tropospheric decrease to 2020. Stratospheric OCS is regressed with simultaneously measured N2O to derive a trend accounting for dynamical variability. Stratospheric lifetimes are derived and range from (54.1 ± 9.7)yr in the sub‐tropics to (103.4 ± 18.3)yr in Antarctica. These unique long‐term measurements provide new and critical constraints on the global OCS budget.
Back‐Arc Dynamics Controlled by Slab Rollback and Tearing: A Reappraisal of Seafloor Spreading and Kinematic Evolution of the Eastern Algero‐Balearic Basin (Western Mediterranean) in the Middle‐Late Miocene
Authors: Haidar Shaza , Déverchère Jacques , Graindorge David , Arab Mohamed , Medaouri Mourad , Klingelhoefer Frauke
Published: January 2022

In spite of clear fan‐shaped magnetic anomalies in the Eastern Algero‐Balearic Basin (EABB), the way how and the time when seafloor spreading occurred are still debated. In this work, a new seismo‐stratigraphic interpretation based on deep‐penetration reflection seismic data correlated to reduced‐to‐the‐pole magnetic anomalies and on‐offshore litho‐stratigraphic correlation of Pre‐Messinian units brings new constraints on its age and mode of opening. Our results reveal that the seafloor spreading of the EABB occurred at an intermediate half‐spreading rate of 3.7 ± 0.5 cm/yr for 2.45 ± 0.18 Myr during the Langhian‐Serravallian times, that is, after the Corsica‐Sardinia block rotation and the collision of Lesser Kabylia with Africa. We revise the kinematics of the Algero‐Balearic domain into three stages: (a) birth of a highly stretched continental basin accommodating the southern drift of the Kabylies driven by slab rollback between ∼23 and ∼15 Ma, (b) fast opening of a new EABB between 15.2 and 12.7 Ma by clockwise rotation of a Greater Alboran Block (GALB) promoted by slab tearing, and (c) late East‐West opening of the western basin in response to the westward retreat of the Gibraltar slab and westward slab tearing propagation and the concomitant migration of the GALB. The last stages match both the late formation of Subduction‐Transform Edge Propagator faults at the toes of the Algero‐Balearic margins and the post‐collisional volcanic migration along the Algerian margin interpreted as related to slab tearing propagation. This new scenario favors a significant stretching and splitting of the GALB into several continental fragments resulting from the westward propagation of the arcuate subduction front by lateral tearing of a narrow slab.
From River to Sea: Estimating Wood Cascades
Authors: Wilke Carolyn
Published: January 2022

Dams and deforestation have chipped away at the millions of cubic meters of wood that flow through rivers and out to sea.
1,2-Acyl migration with α-imino rhodium carbenoids leading to substituted 1-naphthols
Authors: Miura Tomoya , Moritani Shunsuke , Shiratori Yota , Murakami Masahiro
Published: January 2022

Substituted 1-naphthols are synthesised from 2-ethynyl-1-indanones and tosyl azides in one pot. 1,2-Acyl migration occurs with an intermediate α-imino rhodium carbenoid generated from the triazolyl moiety.
Lithium reduction reaction for interfacial regulation of lithium metal anode
Authors: Li Qiuping , Zhang Jiaming , Zeng Yaping , Tang Zheng , Sun Dan , Peng Zhiguang , Tang Yougen , Wang Haiyan
Published: January 2022

This article introduces the recent progress, regulating mechanism and interface characteristics on lithium metal anodes (LMAs) constructed by lithium reduction reactions (LRRs).
Recent advances in electrocatalytic nitrite reduction
Authors: Zhang Xi , Wang Yuting , Wang Yibo , Guo Yamei , Xie Xiaoyun , Yu Yifu , Zhang Bin
Published: January 2022

Electrocatalytic nitrite reduction is of great significance for wastewater treatment and value-added chemicals synthesis.
Antagonistic role of Al3+ against PM2.5-induced neurotoxicity via suppression of NADPH oxidase-triggered oxidative stress
Authors: Liu Fang , Jiang Cuijuan , Liu Rongrong , Yan Bing
Published: January 2022

The relationship between PM2.5 compositions and neuron toxicity was explored and Al3+ was revealed to be antagonistic to other pollutants by decreasing the combined toxic effects.
Simulating intergrowth formation in zeolite crystals: impact on habit and functionality
Authors: Trueman Mollie , Akporiaye Duncan , Anderson Michael W.
Published: January 2022

A kinetic Monte Carlo approach for modelling crystal growth, allowing simulation of crystal habit and surface fine structure in materials containing high levels of stacking faults.
Tuning the efficiency and product composition for electrocatalytic CO2reduction to syngas over zinc films by morphology and wettability
Authors: Li Pengsong , Liu Jiyuan , Bi Jiahui , Zhu Qinggong , Wu Tianbin , Ma Jun , Zhang Farao , Jia Jinchao , Han Buxing
Published: January 2022

The regulation of morphology and wettability of Zn films is an efficient strategy for producing syngas with a wide CO/H2ratio range from electrochemical CO2and H2O reduction.
Capacity sizing of the integrated wind‐solar‐storage system: A nested game approach
Authors: Wang Chuan , Wei Wei , Xie Yuguang , Zheng Tianwen , Mei Shengwei
Published: January 2022

Energy storage (ES) can be a good option to reduce power curtailment and increase the total profits of an integrated energy system. This article addresses the sizing problem for the ES and renewable power plants in the integrated wind‐solar‐storage system (IWSSS). A basic IWSSS model is first constructed to analyze the operation relationship among each part. A nested game model is established to study the capacity sizing problem. The outer layer is a non‐cooperative game among the wind power plant (WPP), the solar power plant (SPP) and the ES. Each of them aims to obtain the maximum revenue which is calculated from the imputation method in the inner cooperative game. This nested game considers both the competitive relationship among three players and the reasonable imputation scheme in the grand system. A nested game algorithm is then proposed to solve this sizing problem and the optimal capacity of each player is found when the Nash equilibrium is achieved. According to the case studies, the optimal capacity ratio of the WPP, the SPP and the ES should be 0.73:0.19:0.08 under the unit transmission line capacity. Results are also conducted to demonstrate the effectiveness of the approach compared with the other two methods.
A sequential hybridization of ETLBO and IPSO for solving reserve‐constrained combined heat, power and economic dispatch problem
Authors: Goudarzi Arman , Fahad Shah , Ni Jiahua , Ghayoor Farzad , Siano Pierluigi , Haes Alhelou Hassan
Published: January 2022

The explosive demand for electricity and ecological concerns has necessitated the operation of power networks in a more cost‐effective approach. In recent years, the integration of combined heat and power units has presented a potential answer to these problems; nevertheless, a new difficult challenge has emerged: finding an optimal solution for simultaneous dispatch of power and heat. Therefore, to tackle this problem, this work presents an intelligent sequential algorithm based on a hybridization of an enthusiasm‐aided teaching and learning‐based optimization algorithm (ETLBO) with an improved version of particle swarm optimization (IPSO). The proposed method can simultaneously minimize total generating costs while considering a variety of physical and operational limitations. In addition, this research designed an adaptive violation constraint management approach combined with the formulated hybridized optimization algorithm to ensure system constraints' safe preservation during the optimization process. Finally, the performance of the proposed method is compared to the recently developed metaheuristic algorithms as well as Knitro and IPOPT (industrially used optimization packages), in which the ETLBO‐IPSO outperforms all the other methods.
Relationship between flow field characteristics and dust collection efficiency of sweeper suction port
Authors: Jin Ye , Jiabao Pan , Hejin Ai , Lujun Zhou
Published: January 2022

Urban pollution caused by road particles is widely criticized. The complex and changeable internal flow field of the dust suction port has the greatest influence of the dust suction operation effect. The aim of this paper is to explore the influence law of various influencing factors on the flow field characteristics of the sweeper’s dust suction port, and reveal its influence mechanism on the dust suction efficiency of the dust suction port. The results of the study show that: increasing the width and outlet diameter will change the flow field characteristics, and the dust suction efficiency will change accordingly, 500 mm and 280 mm are the best width and outlet diameter respectively. The increase of driving speed will increase the relative speed between the inlet surface and dust particles, causing dust particles to spill. The increase of negative pressure at the outlet will increase the flow field characteristics, but the dust suction efficiency will stop when it increases to a certain value. A new dust suction port structure is proposed to further improve the dust suction efficiency. This study can provide a reference for the design of the dust suction port.
Envirronmentally friendly fabrication of Fe2TiO5-TiO2 nanocomposite for enhanced photodegradation of cinnamic acid solution
Authors: Phung Anh Nguyen , Tri Nguyen , Trung Nguyen Dien , Anh Ha Cam , Cuong Hoang Tien , Van Nguyen Thi Thuy , Loc Luu Cam
Published: January 2022

In this study, Fe2TiO5-TiO2 heterostructured composites (FTO-Ti) were synthesised via a simple combination of the sol-gel and hydrothermal methods in a neutral medium of water. Various techniques were used to investigate the characteristics of the FTO-Ti samples, including X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller adsorption (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Vis diffuse reflectance spectroscopy (DRS), and point of zero charges (PZC). Compared to TiO2, the combination of FTO and TiO2 significantly reduces crystal and particle size and increases surface area six-fold, while simultaneously reducing the band gap energy of the catalyst and extending the region of photon absorption zone toward visible wavelengths (407 versus 395 nm). The photocatalytic activity of the FTO-Ti samples was studied using the batch method for the photodegradation of cinnamic acid (CA). The FTO content was found to strongly influence the photocatalytic performance of the FTO-Ti composites. Of the samples studied, 10% FTO-TiO2 nanocomposite exhibits the highest activity for CA decomposition. In the optimum conditions, its maximum 90 min CA conversion reaches 89.0%, which is much higher than both bare Fe2TiO5 (8.5%) and TiO2 (74.8%). Moreover, the catalyst can easily be recovered and reused for at least eight reaction cycles. The results show that hybridising the small band gap Fe2TiO5 pseudobrookite with a large band gap TiO2 semiconductor is a promising approach for the fabrication of highly active photocatalysts.
Immune checkpoint inhibitor-related myocarditis: an illustrative case series of applying the updated Cardiovascular Magnetic Resonance Lake Louise Criteria
Authors: Wintersperger Bernd J , Calvillo-Argüelles Oscar , Lheureux Stephanie , Houbois Christian P , Spreafico Anna , Bedard Philippe L , Neilan Tomas G , Thavendiranathan Paaladinesh
Published: January 2022

Background

Immune checkpoint inhibitors (ICIs) have improved outcomes for many types of cancer. However, ICI therapies are associated with the development of myocarditis, an immune-mediated adverse event associated with a high mortality rate. Therefore, prompt diagnosis and early intervention are of outmost importance. There is limited data on the application of cardiovascular magnetic resonance (CMR)-based modified Lake Louise Criteria (mLLC) with the use of relaxometry techniques for the diagnosis of ICI myocarditis.

Case summary

Four cancer patients undergoing ICI treatment presented with various clinical symptoms and troponin elevation to emergency/ambulatory clinics within 10–21 days after ICI initiation. On the suspicion of possible ICI-related myocarditis all patients underwent CMR within a few days after admission. Applying mLLC including relaxometry techniques, all patients met ‘non-ischaemic injury criteria’, while 3/4 patients met ‘oedema criteria’. In most patients, quantitative mapping revealed substantially increased T1 values, while T2 values were only mildly increased or normal. In two patients with follow-up, CMR demonstrated improvement in findings after immunosuppressive treatment. However, there was only limited agreement between the degree of high-sensitive troponin levels and T1/T2 levels.

Discussion

The application of mLLC with T1/T2 mapping appears useful in the CMR diagnosis of acute ICI myocarditis with non-ischaemic myocardial injury criteria being the most common finding. The sensitivity of native T1 appears higher than T2 mapping in the acute diagnosis as well as in the assessment of treatment response. As troponin elevations may persist for some time with ICI myocarditis, CMR may represent an alternate strategy to monitor treatment response.
AUPHOS, A NOVEL THERAPEUTIC THAT IMPROVES MITOCHONDRIAL FUNCTION AND AMELIORATES CHRONIC COLITIS
Authors: Mohamed Rana , Warinner James , Wempe Lesley , Avdiushko Margarita , Goretsky Tatiana , Kim Jong , Abomhya Ahmed , Lee Goo , Awuah Samuel , Barrett Terrence , Kapur Neeraj
Published: January 2022

BACKGROUND

Inflammatory Bowel Disease (IBD) involves an interplay of gut microbiota, intestinal epithelium and immune responses. Recent data suggest that decreased mitochondrial gene function plays an active role in the pathophysiology of active colitis. Here, we test a novel agent (AuPhos) (Wempe et al., Abstract control ID: 3668199; Crohn’s and Colitis Congress, 2022) that mitigates disease severity in chronic colitis by enhancing mitochondrial function in the gut epithelium.

METHODS

The piroxicam-accelerated (Px) IL-10 KO mouse colitis model was used for testing a novel therapeutic (AuPhos) that increases mitochondrial function in intestinal epithelial cells (IEC). Mice were given Px feeding for 2 weeks (as in Lee et al Gastro, 2010) then treated with AuPhos (25mg/kg) or vehicle every 3d (n=15/group). Disease activity indices (DAI) were calculated (weight loss, diarrhea, and hematochezia) and fecal lipocalin-2 (LCN2) levels (d33-d55) while histological scoring was performed by a blinded GI pathologist (d56). Biopsy samples from consented IBD patients and normal controls were collected in PBS, and treated ex-vivo for 3h with vehicle or AuPhos (0.5uM) at 4oC. Effect of AuPhos on mRNA levels of mitochondrial complexes, cytokine, chemokine and stem cell markers in treated biopsies were examined using RT-qPCR.

RESULTS

Disease activity in Px-IL10 KO mice showed severe colonic inflammation at d48. AuPhos treatment decreased the DAI in Px-IL10 KO mice starting from d31, showing its potential to enhance intestinal wound healing. Histological investigation showed significantly decreased severity of colonic inflammation in AuPhos-treated Px-IL10 KO mice with reductions in overall colitis scores at Day-56 (*; p<0.05). AuPhos treatment also reduced numbers of ulcers and areas of crypt hyperplasia in Px-IL10 KO mice. Further, AuPhos treatment significantly reduced the fecal LCN2 levels at D33 (*; p<0.05), D40 (**; p<0.01) and D55 (*; p<0.05) compared to vehicle treated group. Rt-qPCR analysis of colonic tissue from AuPhos-treated Px-IL10 KO mice showed significant increase in mitochondrial COX1 mRNA compared to vehicle treated mice. Gene expression analysis of human colonic biopsies revealed significant increases in mitochondrial complex I genes (Ndufa1, Ndufa4, Ndufb6), complex IV gene (Cox5B), and stem cell markers (Lgr4, Lgr5, Lrig1), with corresponding decreases in pro-inflammatory markers (IL1β, MCP1, RankL).

CONCLUSION

These data suggest that AuPhos compound improves mitochondrial bioenergetics to prevent inflammation-associated barrier damage under chronic colitis conditions. We believe that AuPhos has an important therapeutic potential to improve ulcer healing and accelerate mucosal repair by restoring mitochondrial metabolism.
ADVERSE CLINICAL OUTCOMES IN PATIENTS WITH ULCERATIVE COLITIS RECEIVING DIFFERENT SEQUENCES OF FIRST- AND SECOND-LINE BIOLOGIC TREATMENTS: FINDINGS FROM ROTARY
Authors: Cleveland Noa , Chastek Benjamin , Ghosh Tito , Candela Ninfa , Bancroft Timothy , Fan Tao , Umashankar Kandavadivu , Rubin David
Published: January 2022

INTRODUCTION

Inadequate response, loss of response, or intolerance to a first-line biologic typically requires patients with ulcerative colitis (UC) to switch treatment to a second-line biologic therapy. However, the clinical outcomes of patients receiving different sequences of biologic treatment are poorly understood. We assessed the adverse clinical outcomes of different treatment sequences.

METHODS

ROTARY (Real wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) part B used data from the Optum Clinical Database and included adult patients diagnosed with UC who received at least two biologics successively between January 1, 2013 and February 29, 2020. This retrospective cohort study measured adverse clinical outcomes, including the incidences of inflammatory bowel disease (IBD)-related hospitalization, IBD-related surgery, dysplasia, colorectal cancer (CRC), and infection during each line of therapy individually and for both lines of treatment overall. The start of the first line of therapy (LOT1) was defined as the date of first prescription or infusion of a biologic therapy. The start of the second line of therapy (LOT2) was defined as the first date of prescription or infusion of a second-line biologic therapy. LOT1 biologics included in the analysis were adalimumab (ADA), infliximab (IFX), and vedolizumab (VDZ). LOT2 biologics included were IFX and ADA.

RESULTS

Among all treatment sequences the overall incidences of hospitalization, surgery, CRC, dysplasia, and infection were lowest for the VDZ to ADA treatment sequence (Figure 1). Patients who received VDZ to IFX had similar overall incidences of adverse outcomes as patients who received two sequential anti-tumor necrosis factor (TNF) therapies (either ADA to IFX or IFX to ADA) (Figure 1). When comparing adverse outcomes during LOT2 there were lower incidences of hospitalization and surgery for the IFX to ADA sequence compared with the ADA to IFX sequence (19.17% vs 23.64% and 7.14% vs 14.24%, respectively) (Table 1). When comparing adverse outcomes on LOT2 for the VDZ to ADA and VDZ to IFX sequences, there were lower incidences of hospitalization and surgery with VDZ to ADA compared with VDZ to IFX (12.50% vs 26.89% and 3.13% vs 22.69%, respectively) (Table 1).

DISCUSSION

In this real-world assessment of biologic treatment sequences in UC, we identified the VDZ to ADA treatment sequence to be associated with the lowest incidence of adverse clinical outcomes. In patients who were unsuccessfully treated with VDZ, ADA as a second-line biologic therapy was associated with lower incidences of adverse clinical outcomes compared with IFX. Although our results could be influenced by selection bias, these data provide potential guidance to clinicians in sequencing biologic therapies in patients with UC.
DOSE ESCALATION OF BIOLOGIC THERAPIES IN BIOLOGIC TREATMENT-NAÏVE ADULT PATIENTS WITH ULCERATIVE COLITIS: RESULTS FROM THE ODESSA DATABASE STUDY
Authors: Kathe Niranjan , Umashankar Kandavadivu , Mirchandani Kirti , Hait Arunima , Paul Riyanka , Ghosh Tito , Candela Ninfa , Fan Tao
Published: January 2022

BACKGROUND

In the real-world clinical setting, patients with moderate-to-severe ulcerative colitis (UC) may undergo dose escalation when they lose response to their prescribed biologic treatment. Such dose escalation of biologic agents has an impact on healthcare utilization and costs and may have an impact on patient outcomes. Currently, limited real-world data exist that compare rates of dose escalation between anti-tumor necrosis factor (anti-TNF) biologic therapies and vedolizumab, a gut-selective integrin antagonist, in patients with UC who have not previously been treated with biologic therapies (bio-naïve patients).

METHODS

ODESSA (real wOrld Dose EScalation and outcomeS with biologics in IBD pAtients) was a retrospective cohort study investigating dose escalation in bio-naïve patients with UC receiving vedolizumab or anti-TNFs (adalimumab, golimumab, and infliximab) using data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases. Adult patients with ≥1 claim for a study drug between January 1, 2017 and December 31, 2018 were selected for inclusion, with the first claim date defined as index date 1 (Figure). Patients were eligible if they had a diagnosis of UC, identified based on UC diagnosis codes, had ≥2 claims for the study drug ≥10 days apart with ≥1 claim on or before index date 1, and had received the study drug for ≥60% of days in the first 6 months after index date 1. Patients were excluded if they had received any biologic treatment before index date 1. The maintenance period began on the date of the third (adalimumab or golimumab) or fourth (infliximab or vedolizumab) pharmacy claim. Dose escalation was defined as a ≥20% increase in mean average daily dose relative to expected daily dose based on the approved prescribing information for UC. The primary endpoint was to compare the proportions of patients experiencing dose escalation of each of the study drugs in the first 6 and 12 months after initiation of maintenance dosing and in the entire maintenance period.

RESULTS

The final analysis cohort included 2,628 patients (vedolizumab, n=554; infliximab, n=758; adalimumab, n=1,316). As a consequence of low patient count, patients treated with golimumab were excluded. At 12 months, the proportion of patients experiencing dose escalation was lowest in the vedolizumab group (36%) and highest in the adalimumab group (44%) (Table).

CONCLUSION

In this retrospective, real-world cohort of bio-naïve patients with UC receiving vedolizumab or anti-TNFs, rates of dose escalation were lowest among patients receiving vedolizumab during the maintenance period. These data seem to indicate that vedolizumab maintains efficacy with less need for dose escalation; however, additional studies are required to investigate dose-escalation requirements for all biologic treatments.
IDENTIFYING THE MOST EFFECTIVE TREATMENT ALGORITHM FOR THERAPIES TO TREAT MODERATE TO SEVERE ULCERATIVE COLITIS
Authors: Scott Frank , Afzali Anita , Dulai Parambir , Lu Mei , Candela Ninfa , Fan Tao , Ghosh Tito , Lewis James
Published: January 2022

BACKGROUND

There has been an ongoing expansion in available biologic and small molecule therapies to treat moderate to severe ulcerative colitis (UC). The sequence in which these therapies are used has been a topic of high interest among clinicians. In the absence of precision medicine for UC, it would be useful to define the sequence of therapies that may predict the best outcomes. Limited data exists regarding the most effective treatment algorithms for achieving optimal patient outcomes. As such, this study endeavors to identify treatment algorithms when considering the UC therapies of vedolizumab, infliximab, ustekinumab, and tofacitinib.

METHODS

A Markov model was used to identify the UC treatment algorithm that would potentially yield the greatest quality adjusted life years (QALYs) over 1 year. The base case was a 35-year old male with moderate to severe UC who had not previously received biologic or immunomodulator therapy. Four medical therapies were considered: (1) infliximab + azathioprine, (2) tofacitinib, (3) ustekinumab, and (4) vedolizumab. Colectomy was assumed to be the least desirable treatment option. These four therapies were combined in eight separate potential treatment algorithms (Figure 1). Tofacitinib was only included after anti-TNF therapy per its USA prescribing indication. With each therapy, simulated individuals could enter remission or response, develop a significant adverse event or infection, or lose response to the therapy. Transition probabilities for response, remission, and adverse event rates were derived from relevant clinical trials. Lymphoproliferative risks were derived from age-specific SEER (Surveillance, Epidemiology, and End Results) data and treatment-specific risks from CESAME. Utility estimates were derived from previously published studies. The time horizon was 1 year. Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts consisting of 100,000 individuals.

RESULTS

Algorithms incorporating vedolizumab as first-line therapy resulted in the greatest quality of life and proportion of patients in remission at 1 year in comparison to strategies where combination therapy with infliximab + azathioprine or ustekinumab were included as first line therapy (Table 1). Vedolizumab followed by infliximab + azathioprine and then ustekinumab resulted in the greatest quality of life advantage. The benefit of this treatment sequence over other sequences ranged from 0.008 to 0.011 QALYs at 1 year.

CONCLUSION

In this model, using vedolizumab prior to infliximab + azathioprine, ustekinumab and tofacitinib is predicted to yield greater quality of life and a greater percentage of patients with clinical remission at the end of 1 year. Further analyses assessing model inputs, probabilistic analyses, and strategy cost-effectiveness are required.
POPULATION PHARMACOKINETICS OF OZANIMOD AND ACTIVE METABOLITE CC112273 IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Shen Jun , Tatosian Daniel , Sid-Otmane Lamia , Teuscher Nathan , Chen Lu , Zhang Peijin , Tirucherai Giridhar , Chitkara Denesh , Marta Cecilia
Published: January 2022

BACKGROUND

Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and moderately to severely active ulcerative colitis (UC) and under development for Crohn’s disease (CD). Following multiple dosing of ozanimod in healthy subjects, ozanimod and two of the active metabolites CC112273 and CC1084037 represent approximately 6%, 73%, and 15% of circulating total active drug exposure, respectively. Two separate pharmacokinetic (PK) models were developed for the most prominent metabolite CC112273 and ozanimod. CC1084037 was not modeled due to the high correlation between CC112273 and CC1084037 plasma concentrations. Therefore, this analysis aims to characterize the PK of ozanimod and the major metabolite CC112273 in UC and RMS population.

METHODS

Subjects from 11 studies (Phase 1 to Phase 3) in healthy volunteers, RMS, and UC patients were included in this population PK analysis. The analyses included a total of 18901 concentrations from 2890 subjects for CC112273 and 18834 PK concentrations from 2977 subjects for ozanimod. A 2-compartment model was used to describe the concentration-time profiles of both ozanimod and CC112273, separately. The influence of weight, age, sex, race, disease, or smoking status and hepatic function on the PK of ozanimod and CC112273 were explored. The impact of concomitant corticosteroids on CC112273 PK were evaluated post hoc.

RESULTS

While the overall apparent clearance of ozanimod was 7% lower in RMS patients compared to UC, similar exposures were observed in both populations. The most influential covariate on ozanimod PK was body weight, with a modest 23% increase in apparent clearance for a 102-kg subject relative to a 70-kg subject (Figure 1). The apparent clearance of CC112273 was 16% greater in RMS patients compared to UC patients, resulting in a slightly higher exposure for UC patients. Increasing body weight had a modest reduction in clearance, while smoking had the largest influence on CC112273 PK of approximately 108% increased clearance (Figure 2). Post-hoc results showed no impact of concomitant prednisone or prednisolone on the PK of CC112273. Other factors, including age, race, sex, or hepatic impairment did not impact the PK of ozanimod or CC112273 PK.

CONCLUSION

The population PK model of CC112273 indicates that covariates with the largest effect on CC112273 PK parameters were body weight and smoking status. However, no covariate impacted clearance by more than 25%. The PK of ozanimod and CC112273 were not meaningfully impacted by age including in the elderly, body weight, race, sex, hepatic function, or concomitant prednisone or prednisolone. Overall, the PK of ozanimod and CC112273 were comparable in UC and RMS patients.