bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP409 Cost-Effectiveness Of Ruxolitinib For Patients With Myelofibrosis: A Review Of The Literature
Authors: Karakuleli Gizem , Barham Leela 
Published: December 2021

IntroductionMyelofibrosis (MF) is a rare (annual incidence estimated to be 1/100,000 in Europe), chronic hematologic disorder associated with morbidity and mortality as well as the risk of evolution to acute myeloid leukemia. Ruxolitinib (Jakavi®, Novartis) is the first JAK 1/2 inhibitor approved by the FDA and EMA in 2011 in treating MF. Ruxolitinib is considered a high-cost and life-time treatment. UK-based estimates of the cost of treatment are in the region of GBP43,000/year/patient (in 2013). Against the background of the challenge of treatments for rare diseases reaching cost-effectiveness thresholds, this study identified, collected, and appraised the available evidence on the cost-effectiveness of ruxolitinib in the treatment of MF.MethodsA systematic approach was taken to conducting the literature review. Databases searched included PubMed, EMBASE, MEDLINE, and the Cochrane Library based on search terms informed by PICO: myelofibrosis, ruxolitinib, best available therapy/standard of care, and cost-effectiveness/cost-utility/pharmacoeconomics. The search was limited to studies published in the English language. A narrative synthesis was used to evaluate studies and the CHEERS checklist to explore the quality of reporting of the cost-effectiveness analysis.ResultsThe narrative synthesis included five studies conducted in the UK, Portugal, Chile, Canada, and Finland. All cost-effectiveness analyses used data from the same two large, randomized controlled, double-blind, phase III studies (COMFORT-I and -II). Ruxolitinib was compared to the best available therapy (BAT), including hydroxyurea, no medication, and prednisone/prednisolone. Perspectives and included costs varied among analyses. Markov models and discrete state cohort models were used to evaluate the cost-effectiveness and clinical benefit was measured in quality-adjusted life years (QALY) or life years (LY) gained.These analyses estimated the base-case incremental cost-effectiveness ratios (ICER) per QALY of (converted into USD, if appropriate, at the historic average annual exchange rate) GBP44,905 in the UK (2013; USD 70,226), EUR40,000 in Portugal (2016; USD44,272), USD54,500 (2016), CAD61,444 in Canada (2012; USD61,474), and EUR42,367 in Finland (2015; USD42,027). Based upon the cost-effectiveness thresholds applied in each of these countries, ruxolitinib was found to be universally cost-effective, albeit with price adjustments as part of the wider pricing and reimbursement processes used in these countries.ConclusionsRuxolitinib was found to be cost-effective in treating MF informed by different types of models and from different perspectives; however, there was some uncertainty around available data due to limited data sources.
PP452 Impact Of Patient Access Schemes On Health Technology Assessment Agency Guidance For Rare Diseases In England and Scotland
Authors: Mark Karen , Manchanda Prachi , Rubinstein Judith , Inumerable Riza Veronica 
Published: December 2021

IntroductionPatient access schemes (PAS) are agreements that may enable patients to access drugs or other treatments that may not be cost effective under normal circumstances. The aim of this study was to determine whether the use of PAS by the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) for recommended drugs can lead to greater access to medications for rare diseases.MethodsReimbursement data for rare diseases between 2004 and 2021 from health technology assessment (HTA) agencies, namely the SMC (Scotland) and NICE (England), were included. The reviews with positive HTA decisions were considered, while those with negative decisions were excluded. Several observations were made from these data and reported.ResultsAmong the total positive reviews (n = 81), 43 included PAS. The inclusion of PAS in manufacturer submissions was more frequent for NICE than for the SMC (79% and 40% percent, respectively). Most of the drugs with PAS were included in the HTA guidance from both agencies. The positive NICE reviews contingent on PAS consisted of 20 drugs. For the same set of drugs, the SMC recommended 14 with PAS and one without PAS; five drugs were not assessed. Adalimumab was recommended by NICE with a PAS (base-case incremental cost-effectiveness ratio of GBP12,336 [EUR14,256]; GBP13,676 [EUR15,804]) and by the SMC without a PAS (base-case incremental cost-effectiveness ratio of GBP22,519 [EUR26,023]). Hence, without a PAS, the drug was costlier per quality-adjusted life-year for the National Health Service (NHS) Scotland.ConclusionsPAS submissions for rare diseases are more frequent for NICE than for the SMC. With the PAS discounts, the overall cost of the drugs is reduced, resulting in cost effectiveness. The SMC approved some drugs for which NICE required a PAS to improve the economic argument. Hence, the use of PAS for these drugs could lead to potential cost-savings to the NHS Scotland.
Exposure to maternal hyperglycemia and high-fat diet consumption after weaning in rats: repercussions on periovarian adipose tissue
Authors: Saullo Carolina M. , Sinzato Yuri K. , Paula Verônyca G. , Gallego Franciane Q. , Corrente José E. , Iessi Isabela L. , Volpato Gustavo T. , Damasceno Débora C. 
Published: December 2021

AbstractClinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.
Planetary‐Scale Waves Seen in Thermal Infrared Images of Venusian Cloud Top
Authors: Kajiwara Naoya , Imamura Takeshi , Taguchi Makoto , Kouyama Toru 
Published: December 2021

AbstractPlanetary‐scale waves are thought to play a crucial role in the maintenance of the atmospheric circulation of Venus. They have been mainly studied using ultraviolet images. In this study, cloud top temperature oscillations associated with planetary‐scale waves were extracted from thermal images taken over 142 Earth days by the Longwave Infrared Camera onboard JAXA's Akatsuki spacecraft. A spectral analysis showed that multiple planetary‐scale waves overlap. The latitudinal structures of four distinct waves with periods of 3.6, 5.0, 5.4, and 6.1 days were studied. The 3.6‐day wave is considered to be a Kelvin wave and the other waves are considered to be hemispherically symmetric Rossby waves. Although the Rossby waves have similar periods, their latitudinal structures are different. The Rossby waves are considered to originate from different sources based on a comparison with analytical solutions.
Effect of Pore‐Scale Heterogeneity on Scale‐Dependent Permeability: Pore‐Network Simulation and Finite‐Size Scaling Analysis
Authors: Ghanbarian Behzad , Esmaeilpour Misagh , Ziff Robert M. , Sahimi Muhammad 
Published: December 2021

AbstractA long‐standing issue in subsurface hydrology and many other related disciplines has been the scaling problem. Although the effect of length scale has been known for years, inconsistent results have been reported in the literature. Experimental data mostly indicate that the permeability k should increase with increasing sample volume, whereas simulations and some theoretical predictions appear to imply the opposite. In this paper, we use the concept of finite‐size scaling to propose a vigorous theoretical framework for addressing the effect of length scale on the permeability. We simulate fluid flow in 12 synthetic and 4 Fontainebleau pore networks to investigate the effect of small‐scale heterogeneities, such as pore‐throat size distribution and pore connectivity. Simulations were carried out for 10 pore coordination numbers, namely, Z = 1.5, 1.65, 1.75, 2, 3, 3.25, 3.5, 4, 5, and 6. For the synthetic pore networks we find a transition in the scale dependence of the permeability, with our results indicating that the permeability increases with the scale for larger pore coordination numbers, whereas the opposite is true for smaller Z. In Fontainebleau pore networks, on the other hand, the trends are decreasing permeabilities regardless of Z. Although the plot of the permeability versus the network size for each pore network appears scattered, through finite‐size scaling analysis the data collapse onto a single quasi‐universal curve. Our results demonstrate that finite‐size scaling analysis is a powerful approach for addressing the effect of length scale on the permeability.
Lateral Flow and Contributing Area Control Vegetation Cover in a Semiarid Environment
Authors: Svoray Tal , Sela Shai , Chen Li , Assouline Shmuel 
Published: December 2021

AbstractSemiarid ecosystems attract attention, because they support the life of large human populations, while functioning under growing threats of degradation due to global climate change that may lead to reduced productivity and possibly irreversible desertification. Empirical support is consequently highly sought after to validate the soil‐moisture‐biomass relationship at the local scale in these ecosystems. Combining physically based models and a database of 32 years of field and remotely sensed data, we examined the effect of soil‐moisture content (SMC) on vegetation cover and patch size distribution in the heterogenous semiarid Lehavim LTER in the Negev Desert, Israel. Results from numerical solutions of flow equations in the shallow soil layer allowed predictions of distributions of SMC as the outcome of vertical and lateral water fluxes. The association of vertical fluxes with patch size distribution and vegetation cover did not support the notion that direct rainfall is sufficient for the shrubs' survival in drought conditions. However, re‐infiltration of downslope runoff, generated in sealed bare intershrub soil area, significantly contributed to the water available to supporting shrub patches. Accordingly, our approach determines potential vegetation cover in semiarid areas, due to the dependency on contributing area and rainfall‐infiltration‐runoff processes. This underscores the fact that, additionally to infiltration from direct rainfall, run‐on contribution controls vegetation cover in semiarid environments. We therefore suggest that estimations of shrub resilience to water stress should consider scenarios involving surface sealing, rainfall duration and intensity, and contributing area size—each in accordance with the contribution of lateral flows to the water available to shrubs.
CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
Authors: Liao Qing , Ren Yun , Yang Yuyi , Zhu Xiaohui , Zhi Yunfei , Zhang Yujie , Chen Yi , Ding Yanqing , Zhao Liang 
Published: December 2021

AbstractLIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.
Precision synthesis of reducing-end thiol-modified cellulose enabled by enzyme selection
Authors: Zhong Chao , Nidetzky Bernd 
Published: December 2021

AbstractEnzyme-catalyzed iterative β-1,4-glycosylation of β-glycosides is promising for bottom-up polymerization of reducing-end-modified cello-oligosaccharide chains. Self-assembly of the chains from solution yields crystalline nanocellulose materials with properties that are tunable by the glycoside group used. Cellulose chains with a reducing-end thiol group are of interest to install a controllable pattern of site-selective modifications into the nanocellulose material. Selection of the polymerizing enzyme (cellodextrin phosphorylase; CdP) was pursued here to enhance the synthetic precision of β-1-thio-glucose conversion to generate pure “1-thio-cellulose” (≥95%) unencumbered by plain (unlabeled) cellulose resulting from enzymatic side reactions. The CdP from Clostridium stercorarium (CsCdP) was 21 times more active on β-1-thio-glucose (0.17 U/mg; 45 °C) than the CdP from Clostridium cellulosi (CcCdP), and it lacked hydrolase activity, which is substantial in CcCdP, against the α-d-glucose 1-phosphate donor substrate. The combination of these enzyme properties indicated that CsCdP is a practical catalyst for 1-thio-cellulose synthesis directly from β-1-thio-glucose (8 h; 25 mol% yield) that does not require a second enzyme (cellobiose phosphorylase), which was essential when using the less selective CcCdP. The 1-thio-cellulose chains had an average degree of polymerization of ∼10 and were assembled into highly crystalline cellulose II crystallinity material.
A crystalline radical cation derived from Thiele’s hydrocarbon with redox range beyond 1 V
Authors: Loh Ying Kai , Vasko Petra , McManus Caitilín , Heilmann Andreas , Myers William K. , Aldridge Simon 
Published: December 2021

AbstractThiele’s hydrocarbon occupies a central role as an open-shell platform for new organic materials, however little is known about its redox behaviour. While recent synthetic approaches involving symmetrical carbene substitution of the CPh2 termini yield isolable neutral/dicationic analogues, the intervening radical cations are much more difficult to isolate, due to narrow compatible redox ranges (typically < 0.25 V). Here we show that a hybrid BN/carbene approach allows access to an unsymmetrical analogue of Thiele’s hydrocarbon 1, and that this strategy confers markedly enhanced stability on the radical cation. 1•+ is stable across an exceptionally wide redox range (> 1 V), permitting its isolation in crystalline form. Further single-electron oxidation affords borenium dication 12+, thereby establishing an organoboron redox system fully characterized in all three redox states. We perceive that this strategy can be extended to other transient organic radicals to widen their redox stability window and facilitate their isolation.
MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge
Authors: Meseda Clement A. , Stauft Charles B. , Selvaraj Prabhuanand , Lien Christopher Z. , Pedro Cyntia , Nuñez Ivette A. , Woerner Amy M. , Wang Tony T. , Weir Jerry P. 
Published: December 2021

AbstractNumerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice. All three MVA vectors induced spike-specific immunoglobulin G after one subcutaneous immunization and serum titers were boosted following a second immunization. The MVA-S and MVA-ssM elicited the strongest neutralizing antibody responses. In assessing protective efficacy, MVA-S-immunized adult Syrian hamsters were challenged with SARS-CoV-2 (USA/WA1/2020). MVA-S-vaccinated hamsters exhibited less severe manifestations of atypical pneumocyte hyperplasia, hemorrhage, vasculitis, and especially consolidation, compared to control animals. They also displayed significant reductions in gross pathology scores and weight loss, and a moderate reduction in virus shedding was observed post challenge in nasal washes. There was evidence of reduced viral replication by in situ hybridization, although the reduction in viral RNA levels in lungs and nasal turbinates did not reach significance. Taken together, the data indicate that immunization with two doses of an MVA vector expressing SARS-CoV-2 S provides protection against a stringent SARS-CoV-2 challenge of adult Syrian hamsters, reaffirm the utility of this animal model for evaluating candidate SARS-CoV-2 vaccines, and demonstrate the value of an MVA platform in facilitating vaccine development against SARS-CoV-2.
Thermal characteristics of longitudinal fin with Fourier and non-Fourier heat transfer by Fourier sine transforms
Authors: Souayeh Basma , Abro Kashif Ali 
Published: December 2021

AbstractThe quest for high-performance of heat transfer components on the basis of accommodating shapes, smaller weights, lower costs and little volume has significantly diverted the industries for the enhancement of heat dissipation with variable thermal properties of fins. This manuscript proposes the fractional modeling of Fourier and non-Fourier heat transfer of longitudinal fin via non-singular fractional approach. The configuration of longitudinal fin in terms of one dimension is developed for the mathematical model of parabolic and hyperbolic heat transfer equations. By considering the Fourier and non-Fourier heat transfer from longitudinal fin, the mathematical techniques of Fourier sine and Laplace transforms have been invoked. An analytic approach is tackled for handling the governing equation through special functions for the fractionalized parabolic and hyperbolic heat transfer equations in longitudinal fin. For the sake of comparative analysis of parabolic verses hyperbolic heat conduction of fin temperature, we depicted the distinct graphical illustrations; for instance, 2-dimensional graph, bar chart, contour graphs, heat graph, 3-dimensional graphs and column graphs on for the variants of different rheological impacts of longitudinal fin.
Tuberculosis trend among native and foreign-born people over a 17 year period (2004–2020) in a large province in Northern Italy
Authors: Marchese Valentina , Rossi Luca , Formenti Beatrice , Magoni Michele , Caruana Anna , Sileo Claudio , Lanfredini Laura , Castelli Francesco , Matteelli Alberto 
Published: December 2021

AbstractTuberculosis (TB) incidence should decline by 20% in the Europe in 2015–2020, in line with End-TB milestones. We retrospectively evaluated TB notifications in the province of Brescia from 2004 to 2020. Cases were classified per patient origin and entitlement to Health Assistance for foreign born people: Italians (ITA), Foreigners permanently entitled (PEF) or Temporarily Entitled (TEF) to Health Regional Assistance. Poisson regression analysis was performed to assess associations between incidence and age, sex, continent of origin and year of notification. Overall 2279 TB cases were notified: 1290 (56.6%) in PEF, 700 (30.7%) in ITA and 289 (12.7%) in TEF. Notifications declined from 15.2/100,000 in 2004 to 6.9/100,000 in 2020 (54.6% reduction, temporary increase in 2013–2018 for TEF). Age (Incidence Risk Ratio, IRR, 1.02, 1.019–1.024 95%CI), sex (IRR 1.22, 1.12–1.34 95%CI), and continent of origin were positively associated with notifications (IRR 34.8, 30.8–39.2 95%CI for Asiatic, and IRR 20.6, 18.1–23.4 95%CI for African origin), p < 0.001. Notification decline was sharper in 2020, especially among TEF. End-TB milestone for 2020 was reached, but foreigners continue to represent a high risk group for the disease. Discontinuation of services due to the COVID-19 pandemic was associated with a sharp decrease in TB notification in 2020.
Modulation of magnetoencephalography alpha band activity by radiofrequency electromagnetic field depicted in sensor and source space
Authors: Wallace Jasmina , Yahia-Cherif Lydia , Gitton Christophe , Hugueville Laurent , Lemaréchal Jean-Didier , Selmaoui Brahim 
Published: December 2021

AbstractSeveral studies reported changes in spontaneous electroencephalogram alpha band activity related to radiofrequency electromagnetic fields, but findings showed both an increase and a decrease of its spectral power or no effect. Here, we studied the alpha band modulation after 900 MHz mobile phone radiofrequency exposure and localized cortical regions involved in these changes, via a magnetoencephalography (MEG) protocol with healthy volunteers in a double-blind, randomized, counterbalanced crossover design. MEG was recorded during eyes open and eyes closed resting-state before and after radiofrequency exposure. Potential confounding factors, known to affect alpha band activity, were assessed as control parameters to limit bias. Entire alpha band, lower and upper alpha sub-bands MEG power spectral densities were estimated in sensor and source space. Biochemistry assays for salivary biomarkers of stress (cortisol, chromogranin-A, alpha amylase), heart rate variability analysis and high-performance liquid chromatography for salivary caffeine concentration were realized. Results in sensor and source space showed a significant modulation of MEG alpha band activity after the radiofrequency exposure, with different involved cortical regions in relation to the eyes condition, probably because of different attention level with open or closed eyes. None of the control parameters reported a statistically significant difference between experimental sessions.