bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating Drug–Target–Drug Complexes in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Switch C5 Inhibitors
Authors: Nishimura Jun‐ichi , Soubret Antoine , Arase Noriko , Buatois Simon , Hotta Masaki , Charoin Jean‐Eric , Ito Yoshikazu , Sreckovic Sasha , Takamori Hiroyuki , Bucher Christoph , Ueda Yasutaka , Hernández‐Sánchez Jules , Gotanda Keisuke , Jordan Gregor , Shinomiya Kenji , Ramos Julia , Kim Jin Seok , Panse Jens , de Latour Régis Peffault , Röth Alexander , Morii Eiichi , Schrezenmeier Hubert , Isaka Yoshitaka , Sica Simona , Kanakura Yuzuru , Yoon Sung‐Soo , Kinoshita Taroh , Paz‐Priel Ido , Sostelly Alexandre 
Published: January 2023

Drug–target–drug complexes (DTDCs) are phenomena newly observed in patients who switch from the complement component 5 (C5) inhibitor eculizumab to crovalimab, a novel, anti‐C5 antibody in development for paroxysmal nocturnal hemoglobinuria (PNH), because these agents bind to different C5 epitopes. In Part 3 of the four‐part, phase I/II COMPOSER study, 19 patients with PNH switching from eculizumab received 1,000‐mg crovalimab intravenously, then subcutaneous maintenance doses from Day 8 (680 mg every 4 weeks (q4w), 340 mg every 2 weeks, or 170 mg every week). Crovalimab exposure was transiently reduced, and size‐exclusion chromatography and crovalimab‐specific enzyme‐linked immunosorbent assays revealed DTDCs in all 19 patients' sera. Additionally, self‐limiting mild to moderate symptoms suggestive of type III hypersensitivity reactions occurred in two patients. Mathematical modeling simulations of DTDC kinetics and effects of dosing on DTDC size distribution using Part 3 data predicted that increased crovalimab concentrations could reduce the proportion of large, slow‐clearing DTDCs in the blood. A simulation‐guided, optimized crovalimab regimen (1,000 mg intravenously; four weekly, subcutaneous 340‐mg doses; then 680 mg q4w from Day 29) was evaluated in Part 4. Confirming the model's predictions, mean proportions of large DTDCs in patients who switched from eculizumab to this optimized regimen decreased by > 50% by Day 22, and target crovalimab concentrations were maintained. No type III hypersensitivity reactions occurred in Part 4. Optimizing crovalimab dosing thus reduced the proportion of large DTDCs, ensured adequate complement inhibition, and may improve safety. Model‐based dosing optimization to mitigate DTDC formation offers a useful strategy for patients switching to novel antibody treatments targeting soluble epitopes.
Transition‐Metal‐Free Unusual Oxidative Cleavage of Homoallylic Alcohol and Its Application in the Upcycling of Terpene to Value‐Added Chemicals
Authors: Lee Tae Woo , Yang Hye Sung , Dawange Monali , Han Young Kwang , Yang Jung Woon 
Published: January 2023

AbstractA NaOtBu−O2‐mediated oxidative dehomologation of homoallylic alcohols into structurally different carboxylic acids through direct oxidative cleavage of either the C(sp2)−C(sp2) or C(sp3)−C(sp3) bond utilizing enolate chemistry was demonstrated. Furthermore, under transition‐metal‐free conditions, this protocol has been applied to convert terpene as biomass feedstock into value‐added chemicals.
Can a mesocarnivore fill the functional role of an apex predator?
Authors: Avrin Alexandra C. , Pekins Charles E. , Wilmers Christopher C. , Sperry Jinelle H. , Allen Maximilian L. 
Published: January 2023

AbstractAs keystone species, apex predators play a role in structuring most ecosystems through competition and facilitation, thereby affecting community structure, prey abundance and behavior, vegetation, and abiotic processes. Apex predators are also highly threatened and have been extirpated from much of North America, leading to mesocarnivores, such as coyotes (Canis latrans), becoming de facto apex predators in many ecosystems. However, it is unknown if these mesocarnivores can fill the same functional keystone role as true apex predators. We compared the spatial and temporal habitat use of mesocarnivores in two similar study systems, one with pumas (Puma concolor) and one without, to determine how the role of coyotes in structuring the carnivore community changes in the absence of pumas. We used multispecies occupancy and relative abundance models to examine the spatial avoidance of pumas and coyotes by the smaller mesocarnivores, and temporal overlap and avoidance‐attraction ratios to examine temporal avoidance. We found that coyotes partially fill the functional role of apex predators, but with weaker effects than pumas. Where pumas were absent, site use intensity and relative abundance increased for coyotes (180% and 1250%) and raccoons (Procyon lotor, 308% and 3273%) and decreased for bobcats (Lynx rufus, 36% and 55%), gray foxes (Urocyon cinereoargenteus, 13% and 32%), and striped skunks (Mephitis mephitis, 3% and 12%). Coyotes and raccoons shifted their temporal activity away from pumas, while gray foxes shifted their activity closer to pumas. Detection likelihood decreased for all species after detection of a puma (67%–93%) or coyote (46%–94%) in both sites, but small mesocarnivores avoided pumas more than coyotes in the study area with both. Interactions between carnivores are complex and best understood with multiple measures and in the context of the full community. While coyotes appear to suppress smaller mesocarnivores by some measures (e.g., temporal avoidance), they do not by others (e.g., spatial avoidance) and have overall weaker effects than pumas. Our results suggest that coyotes are not a substitute for apex predators, and conserving true apex predators is likely important for maintaining ecosystem health.
Seasonal variations in nutritive and botanical composition properties of multispecies grazing swards over an entire dairy grazing season
Authors: Hearn Ciarán , Egan Michael , Lynch Mary Bridget , Fleming Christina , O'Donovan Michael 
Published: January 2023

AbstractBackgroundRecently, there has been increasing interest in the use of multispecies (MS) swards in dairy grazing systems.MethodsA plot grazing study was established to investigate the potential contribution of different sward species (perennial ryegrass, legumes and herbs) sown in grazing pastures. Ten sward mixtures were sown, ranging in complexity from a perennial ryegrass (PRG) monoculture to binary mixtures including either forage legumes or herbs to a five‐species mixture; four different nitrogen (N) application rates of 0, 100, 150 and 200 kg N ha−1 were applied to each sward.ResultsSpecies abundance for all sward species components was associated with the interaction of time point and sward mixture; species abundance for all sward components, except PRG, was associated with the interaction of N application and sward mixture. The interactions of time point and sward mixture, and time point and N application rate, were associated with all analysed sward chemical components, except for sward digestibility.ConclusionsIncreased N application rates reduced the level of clover in all sward mixtures. Increased levels of white clover led to increased sward crude protein levels; the inclusion of ribwort plantain led to some seasonal variation in the nutritive value of swards.
Efficacy and safety of novel pulsed field ablation (PFA) technique for atrial fibrillation: A systematic review and meta‐analysis
Authors: Shaheen Nour , Shaheen Ahmed , Ramadan Abdelraouf , Nashwan Abdulqadir J. 
Published: January 2023

AbstractBackground and AimPulse field ablation (PFA) has emerged as a safe alternative to other catheter ablation energy sources for patients. Although early results are encouraging, secondary data about outcomes are lacking. Herein, we aimed to assess the safety and efficacy of the novel technique.MethodsWe searched PubMed, Ovid, Google Scholar, Web of Science, and Scopus databases and several major scientific conferences for studies reporting results regarding PFA.ResultsSixteen studies were included, reporting 485 patients with atrial fibrillation who underwent pulsed field operations. Patients averaged 60 years of age. The total duration of the procedure is 94 min. The average Fluoro procedure takes 17 min. Isolation of all pulmonary veins was 100% with a 95% confidence interval (CI) (p > 0.05). Overall, the recurrence rate of arrhythmia in the participants was 2.84% (95% CI) (p > 0.05). Complications were detected during or after the PFA procedure at a rate of 2.23% (p < 0.05), with 95% CI indicating the high safety of the PFA procedureConclusionUsing pulsed‐field ablation as a new treatment for atrial fibrillation has proven safe and effective.
Cavity inclination effect on convection flow in a triangular geometry
Authors: Elguennouni Youssef , Hssikou Mohamed , Baliti Jamal , Alaoui Mohammed 
Published: January 2023

AbstractIn this study, the water convection flow within a right‐angled, inclined, and isosceles triangle enclosure for various inclination angles was numerically analyzed using the lattice Boltzmann method with the multirelaxation time model. On the hypotenuse side, the enclosure is thermally insulated, while the left and horizontal walls are kept, respectively, at cold and hot temperatures. This study was conducted to show the effects of two key parameters, the tilt angle and the Rayleigh number , whose changes span from to and to , respectively. The effect of these variables is presented in terms of streamlines, isotherms, velocity profiles, temperature plots, and the average Nusselt number. Furthermore, the impact of the size of a hot square obstruction inside the cavity on the isotherms and streamlines has been investigated. The findings demonstrate that the rate of heat transport is enhanced as the Rayleigh number increases. This result is in good agreement with earlier research without tilting the cavity. Depending on the Rayleigh number, the tilt angle has a significant effect on the rate of heat transmission.
Numerical investigation of large‐scale seasonal rock‐pit energy storage system
Authors: Pinto Samson P. , Dandagawhal Piyush , Sasmito Agus P. , Lacey Joshua 
Published: January 2023

AbstractA twodimensional axisymmetric model, which is computationally inexpensive, has been proposed to predict the property changes that occur in a seasonal rock‐pit energy storage (RPES) system. The geometry of the rock‐pit has been simplified into a shape that can be extended for any seasonal storage system with a three‐dimensional conical geometry. The computational domain has been solved using both linear thermal equilibrium (LTE) and linear thermal non‐equilibrium (LTNE) models, and the former has been found to be computationally quick and accurate. The model has predicted a 95% energy saving at the highest flow conditions required in the mine. Further analysis has suggested that the increase in storage capacity by decreasing the porosity of rocks in the rock‐pit is insignificant compared to the corresponding increase in fan power. Furthermore, the investigation done on natural rocks has indicated an increased ability to store heat in the rock‐pit when rocks with higher thermal mass have been used. The use of RPES has shown a significant potential to reduce the carbon footprint. Finally, an economic analysis done on the system has shown a return on investment of just under 12 years.
Expected Benefits and Budget Impact From a Microsimulation Model Support the Prioritization and Implementation of Fracture Liaison Services
Authors: Pinedo-Villanueva Rafael , Burn Edward , Maronga Christopher , Cooper Cyrus , Javaid M Kassim 
Published: January 2023

ABSTRACT
Osteoporotic-related fractures cause significant patient disability, leading to a growing burden on health care systems. Effective secondary fracture prevention can be delivered by fracture liaison services (FLSs), but these are not available in most countries. A major barrier is insufficient policy prioritization, helped by the lack of economic assessments using national data and providing estimates of patient outcomes alongside health care resource use and cost impacts. The aim of this study was to develop an economic model to estimate the benefits and budget impact of FLSs and support their wider international implementation. Five interconnected stages were undertaken: establishment of a generic patient pathway; model design; identification of model inputs; internal validation and output generation; and scenario analyses. A generic patient pathway including FLS activities was built to underpin the economic model. A state-based microsimulation model was developed to estimate the impact of FLSs compared with current practice for men and women aged 50 years or older with a fragility fracture. The model provides estimates for health outcomes (subsequent fractures avoided and quality-adjusted life years [QALYs]), resource use, and health and social care costs, including those necessary for FLSs to operate, over 5 years. The model was run for an exemplar country the size of the United Kingdom. FLSs were estimated to lead to a reduction of 13,149 subsequent fractures and a gain of 11,709 QALYs. Hospital-bed days would be reduced by 120,989 and surgeries by 6455, while 3556 person-years of institutional social care would be avoided. Expected costs per QALY gained placed FLSs as highly cost-effective at £8258 per QALY gained over the first 5 years. Ten different scenarios were modeled using different configurations of FLSs. Further work to develop country-specific models is underway to delivery crucial national level data to inform the prioritization of FLSs by policy makers. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial
Authors: Pérez-Castrillón José Luis , Dueñas-Laita Antonio , Gómez-Alonso Carlos , Jódar Esteban , del Pino-Montes Javier , Brandi Maria Luisa , Cereto Castro Fernando , Quesada-Gómez José Manuel , Gallego López Laura , Olmos Martínez José Manuel , Alhambra Expósito María Rosa , Galarraga Bernat , González-Macías Jesús , Neyro José Luis , Bouillon Roger , Hernández-Herrero Gonzalo , Fernández-Hernando Nieves , Chinchilla Sandra P. 
Published: January 2023

ABSTRACT
Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D &lt; 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Mesoscale eddies with anomalous sea surface temperature and its relation with atmospheric convection over the North Indian Ocean
Authors: Gulakaram Venkata Sai , Vissa Naresh Krishna , Bhaskaran Prasad Kumar 
Published: January 2023

AbstractMesoscale eddies are the important phenomenon of world oceans that play a prominent role in influencing the near‐surface atmosphere and transport of heat. Ocean and atmosphere responses due to the presence of oceanic mesoscale eddies are not well studied in the Northern Indian Ocean (NIO) region. The present study analysed the ocean and atmospheric response due to the presence of mesoscale eddies using a composite analysis. Generally, it is assumed that the anti‐cyclonic eddies are associated with the positive anomalies of sea surface temperature (SST), and cyclonic eddies are accompanied by negative anomalies. However, for the two marginal seas in the NIO, that is, the Bay of Bengal (BoB) and Arabian Sea (AS), the composite picture of SST anomalies associated with mesoscale eddies showed an abnormal response of SST. This unusual behaviour of cold SST near anti‐cyclonic eddies and warm SST near cyclonic eddies in BoB and AS is analysed with the mean composites of precipitation, outgoing longwave radiation (OLR), and turbulent fluxes. The mean composites over all anti‐cyclonic eddies reveal the presence of enhanced precipitation and convection (low OLR), whereas over cyclonic eddies, suppressed convection and negative precipitation anomalies are evident. The composites of latent heat flux (LHF), precipitation and OLR near surface cold anti‐cyclonic eddies indicate the loss of heat from the ocean to the atmosphere, intense precipitation along with cloudy conditions are responsible for the cooling of the ocean. Along with this, stronger winds are also evident during cloudy conditions could play a role in anomalous cooling of SST observed near anti‐cyclonic through intense surface mixing. Similarly, vice versa is observed near the surface warm cyclonic eddies. The overlying atmosphere and abnormal response of SST near oceanic eddies are essential for understanding the significant role of oceanic mesoscale eddies in influencing the large‐scale circulation of the atmosphere and climate.
Effects of heating rates on the self‐assembly behavior and gelling properties of beef myosin
Authors: Fang Tian , Han Mengfan , Wang Yue , Xiang Xiaomei , Chen Lin , Yang Huijuan , Kang Zhuangli , Huang Feng , Fan Xiaojing , Han Minyi , Xu Xinglian , Zhou Guanghong , Ullah Niamat , Feng Xianchao 
Published: January 2023

AbstractBACKGROUNDMyosin is the most important component of myofibrillar protein, with excellent gelling properties. To date, heating treatment remains the mainstream method for forming gel in meat products, and it has the most extensive application in the field of meat industry. However, at present, there are few reports on the effects of heating rates on myosin self‐assembly and aggregation behavior during heating treatment.RESULTSThe present study aimed to investigate the effects of different heating rates (1, 2, 3 and 5 °C min−1) on the self‐assembly behavior, physicochemical, structural and gelling properties of myosin. At the lowest heating rate of 1 °C min−1, the myosin gel had a dense microstructure, the highest elastic modulus (G′) and water holding capacity compared to higher heating rates (2, 3 and 5 °C min−1). At higher temperatures (40, 45 °C), the surface hydrophobicity, turbidity, particle size distribution and self‐assembly behavior of myosin in pre‐gelling solutions showed that myosin had sufficient time to denature, underwent full structure unfolding before aggregation at the heating rate of 1°C min−1, and formed regular and homogeneous spherical aggregates. Therefore, the myosin gel also had a better three‐dimensional network.CONCLUSIONThe heating rates had an important effect on the quality of myosin gels, and had theoretical implications for improving the quality of meat gel products. © 2023 Society of Chemical Industry.
Interfacial Interaction Enables Enhanced Mobility in Hybrid Perovskite‐Conjugated Polymer Transistors with High‐k Fluorinated Polymer Dielectrics
Authors: Nketia‐Yawson Vivian , Nketia‐Yawson Benjamin , Jo Jea Woong 
Published: January 2023

AbstractThe charge carrier mobility of organic field‐effect transistors (OFETs) has been remarkably improved through several engineering approaches and techniques by targeting pivotal parts. Herein, an ultrathin perovskite channel layer that boosts the field‐effect mobility of conjugated polymer OFETs by forming perovskite‐conjugated polymer hybrid semiconducting channel is introduced. The optimized lead‐iodide‐based perovskite‐conjugated polymer hybrid channel transistors show enhanced hole mobility of over 4 cm2 V–1 s–1 (average = 2.10 cm2 V–1 s–1) with high reproducibility using a benchmark poly(3‐hexylthiophene) (P3HT) polymer and employing high‐k fluorinated polymer dielectrics. A significant hole carrier mobility enhancement of ≈200–400% in benzo[1,2‐b:4,5:b′]dithiophene (BDT)‐based conjugated polymers is also demonstrated by exploring certain interactive groups with perovskite. This significant enhancement in the transistor performance is attributed to the increased charge carrier density in the hybrid semiconducting channel and the perovskite–polymer interactions. The findings of this paper demonstrate an exceptional engineering approach for carrier mobility enhancement in hybrid perovskite‐conjugated‐polymer‐based electronic devices.
Proof‐of‐concept for incorporating mechanistic insights from multi‐omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae
Authors: Hanafin Patrick O. , Abdul Rahim Nusaibah , Sharma Rajnikant , Cess Colin G. , Finley Stacey D. , Bergen Phillip J. , Velkov Tony , Li Jian , Rao Gauri G. 
Published: January 2023

AbstractCarbapenemase‐resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time‐kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism‐based model (MBM) was developed using time‐kill data in S‐ADAPT describing PMB‐CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax: 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one‐compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi‐omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi‐omics responses via a multi‐omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2 = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi‐omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.