bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Bioequivalence of 2 Safinamide Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Li Xin , Wen Jing , Liu Yujie , Xu Bing , Li Yuan , Li You , Zhang Ping , Li Xianjing 
Published: September 2022

AbstractTo assess the bioequivalence of a generic safinamide tablet (test) vs a brand‐name safinamide tablet (reference) and effects of food on the pharmacokinetics of safinamide in healthy Chinese subjects, a single‐center, single‐dose, randomized, open‐label, 2‐preparation, 2‐period study with a 15‐day washout period was undertaken. A total of 56 healthy subjects were recruited in this study (fasting, n = 28; fed, n = 28). A single dose of a 100‐mg test or reference safinamide tablet was administered to each subject in a randomized sequence. Blood samples were obtained at 5 minutes before drug administration and during the 120 hours after dosing. The safinamide concentration in plasma was determined by high‐performance liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were analyzed with noncompartmental methods. Safety was also monitored. The major pharmacokinetic parameters including maximum plasma drug concentration, area under plasma concentration‐time curve (AUC) from zero to time t (AUC0‐t), and AUC from time 0 to infinity (AUC0‐∞) were similar between the test and reference tablets under fasting and fed conditions. The 90% CIs of the test/reference ratios of log‐transformed maximum plasma drug concentration, AUC from zero to time t, and AUC from time 0 to infinity all fell within the equivalence interval (80.0%‐125%) whether under fasting condition or fed condition. In conclusion, the 2 formulations of safinamide tablets were bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. High‐fat food delayed the absorption of safinamide but did not affect the final bioavailability.
Phosphorous NMR Analysis and Activity of Chiral BINAP‐Silver Complexes
Authors: Plevová Kristína , Prieto Pabon Laura Juliana , Gaysinski Marc , Poulain‐Martini Sophie , Michelet Véronique 
Published: September 2022

AbstractChiral Ag‐atropisomeric ligand species were studied in solution at different temperatures by 31P‐NMR spectroscopy. The analysis and understanding of key parameters in Ag‐BINAP complexes were considered in the context of an enantioselective transformation. An efficient silver‐catalyzed intramolecular [4+2] cycloaddition reaction of amide‐1,6‐enyne provided an enantiomerically enriched tricyclic compound using simple reagents and under mild reaction conditions.
Studying Telmisartan Plasma Exposure, Kidney Distribution, Receptor Occupancy, and Response in Patients With Type 2 Diabetes Using [11C]Telmisartan
Authors: van der Hoek Sjoukje , Mulder Douwe J. , Willemsen Antoon T.M. , Visser Ton , Heeres Andre , Slart Riemer H.J.A. , Elsinga Philip H. , Heerspink Hiddo J.L. , Stevens Jasper 
Published: September 2022

The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin‐1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary‐albumin‐to‐creatinine‐ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = −0.64, P = 0.046, median change UACR: −40.1%, 95% confidence interval (CI): −22.9 to −77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin‐1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [11C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC0–last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.
Salivary Areca and tobacco alkaloids for bioverification in the Betel Nut Intervention Trial
Authors: Franke Adrian A. , Li Xingnan , Herzog Thaddeus A. , Paulino Yvette C. , Badowski Grazyna , Wilkens Lynne R. , Lai Jennifer F. 
Published: September 2022

AbstractBackgroundThe Betel Nut Intervention Trial (BENIT) is the first known randomized controlled intervention trial designed to help minority Pacific Islanders in Guam and Saipan quit chewing the carcinogenic Areca catechu nut (AN). We report the BENIT's saliva bioverification results against the self‐reported chewing status (“quitter” or “chewer”) at day 22 follow‐up.Material and MethodsAN‐specific (arecoline, arecaidine, guvacoline, and guvacine) and tobacco‐specific (nicotine, cotinine, and hydroxycotinine) alkaloids were analyzed in saliva from 176 BENIT participants by an established and sensitive liquid chromatography mass spectrometry‐based assay.ResultsThe combined four AN alkaloid levels decreased from baseline in quitters (n = 50) and chewers (n = 108) by 32% and 9%, respectively. In quitters, decreases were significant for arecoline (p = 0.044)—the most prominent AN alkaloid, along with arecaidine (p = 0.042) and nicotine (p = 0.011). In chewers, decreases were significant only for hydroxycotinine (p = 0.004). Similar results were obtained when quitters and chewers were stratified by treatment arm.DiscussionSalivary AN alkaloid levels generally agreed with self‐reported chewing status, which suggests the former can be used to verify the latter.ConclusionOur results can help to objectively evaluate compliance and program effectiveness in AN cessation programs.
Glypican‐6 and Glypican‐4 stimulate embryonic stomach growth by regulating Hedgehog and noncanonical Wnt signaling
Authors: Shi Wen , Filmus Jorge 
Published: September 2022

AbstractBackgroundGlypicans are a family of proteoglycans that play important roles in embryonic morphogenesis. The mammalian genome contains six glypicans (GPC1 to GPC6). GPC6 and GPC4 are the pair of glypicans that show the highest degree of homology within the family. GPC6‐null embryos display bone abnormalities and severely shortened intestines.ResultsWe show that GPC6‐null embryos display significantly smaller stomachs, and that Hedgehog and noncanonical Wnt signaling are dysregulated in GPC6‐null stomachs. Like GPC6, GPC4 is expressed by the developing stomach. However, GPC4‐null embryos have normal stomachs. To investigate whether GPC6 and GPC4 display functional overlap in the developing stomach, we crossed GPC4‐null mice with GPC6 conditional mutants in which the expression of this glypican is severely reduced in the stomach. Notably, we found that the compound mutants display stomachs that are smaller than those of the GPC6 conditional mutants. We also found that this functional overlap between GPC6 and GPC4 is mediated by the noncanonical Wnt pathway.ConclusionThis study demonstrates that GPC6 stimulates the growth of the embryonic stomach via Wnt and Hh signaling. In addition, we uncovered a Wnt‐mediated functional overlap between GPC6 and GPC4 in the developing stomach.
Ventricular anisotropic deformation and contractile function of the developing heart of zebrafish in vivo
Authors: Salehin Nabid , Teranikar Tanveer , Lee Juhyun , Chuong Cheng‐Jen 
Published: September 2022

AbstractBackgroundThe developing zebrafish ventricle generates higher intraventricular pressure (IVP) with increasing stroke volume and cardiac output at different developmental stages to meet the metabolic demands of the rapidly growing embryo (Salehin et al. Ann Biomed Eng, 2021;49(9): 2080‐2093). To understand the changing role of the developing embryonic heart, we studied its biomechanical characteristics during in vivo cardiac cycles. By combining changes in wall strains and IVP measurements, we assessed ventricular wall stiffness during diastolic filling and the ensuing systolic IVP‐generation capacity during 3‐, 4‐, and 5‐day post fertilization (dpf). We further examined the anisotropy of wall deformation, in different regions within the ventricle, throughout a complete cardiac cycle.ResultsWe found the ventricular walls grow increasingly stiff during diastolic filling with a corresponding increase in IVP‐generation capacity from 3‐ to 4‐ and 5‐dpf groups. In addition, we found the corresponding increasing level of anisotropic wall deformation through cardiac cycles that favor the latitudinal direction, with the most pronounced found in the equatorial region of the ventricle.ConclusionsFrom 3‐ to 4‐ and 5‐dpf groups, the ventricular wall myocardium undergoes increasing level of anisotropic deformation. This, in combination with the increasing wall stiffness and IVP‐generation capacity, allows the developing heart to effectively pump blood to meet the rapidly growing embryo's needs.
Seabirds subsidize terrestrial food webs and coral reefs in a tropical rat‐invaded archipelago
Authors: Linhares Bruno de Andrade , Bugoni Leandro 
Published: September 2022

AbstractAllochthonous resource fluxes mediated by organisms crossing ecosystem boundaries may be essential for supporting the structure and function of resource‐limited environments, such as tropical islands and surrounding coral reefs. However, invasive species, such as black rats, thrive on tropical islands and disrupt the natural pathways of nutrient subsidies by reducing seabird colonies. Here, we used stable isotopes of nitrogen and carbon to examine the role of seabirds in subsidizing the terrestrial food webs and adjacent coral reefs in the Abrolhos Archipelago, Southwest Atlantic Ocean. By sampling invasive rats and multiple ecosystem compartments (soil, plants, grasshoppers, tarantulas, and lizards) within and outside seabird colonies, we showed that seabird subsidies led to an overall enrichment in 15N across the food web on islands. However, contrary to other studies, δ15N values were consistently lower within the seabird colonies, suggesting that a higher seabird presence might produce a localized depletion in 15N in small islands influenced by seabirds. In contrast, the nitrogen content (%N) in plants and soils was higher inside the colonies, corresponding to a higher effect of seabirds at the base of the trophic web. Among consumers, lizards and invasive rats seemed to obtain allochthonous resources from subsidized terrestrial organisms outside the colony. Inside the colony, however, they showed a more direct consumption of marine matter, suggesting that subsidies benefit these native and invasive animals both directly and indirectly. Nonetheless, in coral reefs, scleractinian corals assimilated seabird‐derived nitrogen only around the two smaller and lower‐elevation islands, as demonstrated by the substantially higher δ15N values in relation to the reference areas. This provides evidence that island morphology may influence the incorporation of seabird nutrients in coral reefs around rat‐invaded islands, likely because guano lixiviation toward seawater is facilitated in small and low‐elevation terrains. Overall, these results showed that seabirds affected small islands across all trophic levels within and outside colonies and that these effects spread outward to coral reefs, evidencing resiliency of seabird subsidies even within a rat‐invaded archipelago. Because rats are consumers of seabird chicks and eggs, however, rat eradication could potentially benefit the terrestrial and nearshore ecosystems through increased subsides carried by seabirds.
Feast or famine: How is global change affecting forage supply for Yellowstone's ungulate herds?
Authors: Frank Douglas A. , Becklin Katie M. , Penner Jacob F. , Lindsay K. Alice , Geremia Chris J. 
Published: September 2022

AbstractThe ecological integrity of US national parks and other protected areas are under threat in the Anthropocene. For Yellowstone National Park (YNP), the impacts that global change has already had on the park's capacity to sustain its large migratory herds of wild ungulates is incompletely understood. Here we examine how two understudied components of global change, the historical increase in atmospheric CO2 and the spread of nonnative, invasive plant species, may have altered the capacity of YNP to provide forage for ungulates over the last 200‐plus years. We performed two experiments: (1) a growth chamber study that determined the growth rates of important invasive and native YNP grasses that are forages for ungulates under preindustrial (280 ppm) versus modern (410 ppm) CO2 levels and (2) a field study that compared the effect of defoliation (clipping) on the shoot growth of invasive and native mesic grassland plants under ambient CO2 conditions in 2019. The growth chamber experiment revealed that modern CO2 increased the growth rates of both invasive and native grasses, and invasive grasses grew faster regardless of CO2 conditions. The field results showed a continuum of positive to negative responses of shoot growth to defoliation, with a subgroup of invasive species responding most positively. Altogether the results indicated that the historical increase in CO2 and the spread of invasive species, some of which were planted to provide forage for ungulates in the early and mid‐1900s, have likely increased the capacity of forage production in YNP. However, rising CO2 has also resulted in regional warming and increased aridity in YNP, which will likely reduce grassland productivity. The challenge for global change biologists and park managers is to determine how competing components of global change have already affected and will increasingly affect forage dynamics and the sustainability of Yellowstone's iconic ungulate herds in the Anthropocene.
Temporal shifts in avian phenology across the circannual cycle in a rapidly changing climate: A global meta‐analysis
Authors: Romano Andrea , Garamszegi László Zsolt , Rubolini Diego , Ambrosini Roberto 
Published: September 2022

AbstractThe alteration of the timing of biological events is one of the best documented effects of climate change, with overwhelming evidence across taxa. Many studies have investigated the phenology of consumers, especially birds. However, most of these studies have focused on specific phenophases, whereas a global analysis of avian phenological trends during recent climate change across different phases of the circannual cycle is still lacking. Here, we performed a comprehensive meta‐analytic synthesis of the phenological responses (temporal shifts in days year−1) of birds across different phenophases (prebreeding migration, breeding, and postbreeding migration) by summarizing more than 5500 time series from 684 species from five continents during 1811–2018. Our results confirm that avian taxa have advanced prebreeding migration and breeding by ~2–3 days per decade, whereas no significant temporal changes in the timing of postbreeding migration were documented. Advancement in the timing of prebreeding migration and breeding strongly depended on migratory behavior, with the advance being the weakest for long‐distance migrants and the strongest for resident species. Diet generalists and primary consumers tended to advance prebreeding migration timing more than species with different dietary specializations. Increasing body size resulted in a larger advancement in the onset (but not in the mean date) of prebreeding migration and breeding, whereas phenological advances were larger in the northern than in the southern hemisphere. Our synthesis, covering most of the world, highlighted previously unappreciated patterns in avian phenological shifts over time, suggesting that specific life‐history or ecological traits may drive different responses to climate change.
Effects of Drying Conditions on the Content of Biologically Active Compounds in Winter Camelina Sativa Seeds
Authors: Gawrysiak‐Witulska Marzena , Siger Aleksander , Grygier Anna , Rusinek Robert , Gancarz Marek 
Published: September 2022

AbstractThe moisture content of Camelina sativa seeds has to be maintained at 7–12% during storage in order to preserve their quality. If seeds with higher moisture contents are to be stored, they first need to be dried. This study presents the effects of high‐temperature drying (at 40, 60, 80, 100, 120, and 140 °C) of C. sativa seeds on the technological usefulness (expressed as the acid value) and bioactive compound content (as polyenoic fatty acid, vitamin‐E active compounds, and phytosterols). It is shown that drying temperature significantly affects levels of bioactive compounds. Losses of phytosterols reached a maximum of 24% (for temperatures in the 80–140 °C range), while losses of tocopherols range from 2–11%, depending on cultivar. A change in the percentage composition of polyenoic acids is observed upon air drying at 100–140 °C. It is recommended not to exceed 60 °C when drying C. sativa seeds, in order to guarantee that high‐quality cold‐pressed oil with high levels of bioactive compounds is obtained.Practical application: The seeds of Camelina sativa, like other oilseeds, require appropriate storage after harvesting in order to maintain continuity of production. Maintaining the high seed quality during storage requires drying them after harvesting to a moisture content of 7–12%. Drying conditions have a significant effect on seed quality, expressed as acid number, and also affect the levels of bioactive compounds (such as polyene fatty acids, tocopherols, plastochromanol‐8, and phytosterols) in the oil. Information on optimum drying conditions will contribute to the availability of high‐quality camelina oils produced by small local manufacturers.
Changes in Emulsifying and Physical Properties of Shrimp Oil/Soybean Oil‐in‐Water Emulsion Stabilized by Fish Myofibrillar Protein during the Storage
Authors: Rajasekaran Bharathipriya , Singh Avtar , Zhang Bin , Hong Hui , Benjakul Soottawat 
Published: September 2022

AbstractProperties of shrimp oil/soybean oil (30:70)‐in‐water emulsion stabilized using fish myofibrillar protein (FMP) at different concentrations (15, 30, and 45 mg mL−1) are investigated. When FMP concentration increases, emulsion activity index decreases (p < 0.05). Conversely, emulsion stability index, adsorbed protein, and interfacial protein contents are augmented (p < 0.05). During storage of 15 days, emulsion added with FMP at 45 mg mL−1 (FMP‐45) has the highest turbidity, zeta potential, viscosity, and viscoelastic properties (G′ and G″) than the others (p < 0.05). Emulsions show shear‐thinning and non‐Newtonian behavior. The emulsion added with FMP at 15 and 30 mg mL−1 (FMP‐15 and FMP‐30, respectively) has dominant viscous properties (G′ < G″), whereas FMP‐45 shows elastic gel‐like behavior (G′ > G″) (p < 0.05). Lower droplet size (d32 and d43), polydispersity index (PDI), flocculation (Fi), and coalescence (Ci) are observe in FMP‐45 (p < 0.05). Microstructure reveals smaller droplet size and smaller increase in droplet size of FMP‐45 after storage. Overall, all emulsions remain stable with no obvious phase separation throughout the storage. Confocal laser scanning microscopic images show that increase in FMP concentration can yield monodisperse emulsion. Therefore, fish myofibrillar protein exhibits excellent emulsifying property and stability for shrimp/soybean oils‐in‐water emulsion.Practical Applications: Oil from shrimp hepatopancreas, a byproduct from hepatopancreas free whole shrimp, is well known for their health benefits. It can be used to produce functional food emulsion such as mayonnaise. The use of fish myofibrillar protein is proven to be a potential emulsifier, which can improve emulsifying properties. The obtained emulsion is stable without no phase separation during the extended storage. This finding can be beneficial for food industries to produce food emulsion rich in high quality protein and polyunsaturated fatty acid. Also, hepatopancreas can be fully exploited.
A Long‐Lasting Skin Protectant Based on CG‐101, a Deep Eutectic Solvent Comprising Choline and Geranic Acid
Authors: Shevachman Marina , Mandal Abhirup , Gelston Kevin , Mitragotri Samir , Joshi Nitin 
Published: September 2022

AbstractThe COVID‐19 public health crisis has spotlighted the need to improve global hygiene and sanitization. In addition to causing staggering rates of transmission and fatality, COVID‐19 has severely impacted the quality of life and mental health of global citizens. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) encourage hand hygiene as the first defense against the spread of infection, yet frequent handwashing is often impractical. Widely used ethanol‐based hand sanitizers provide immediate protection against pathogens on the skin, albeit short‐lived, due to their rapid evaporation. Herein, a novel, long‐lasting skin protectant formulated with biocompatible ionic liquid/deep eutectic solvents prepared using generally recognized as safe materials – choline and geranic acid (CG‐101, 5% w/w) – is described. In vitro studies demonstrated that CG‐101 inactivates bacteria and the human coronavirus, hCoV229E, for 4 h after application. Two human clinical studies demonstrate that CG‐101 does not cause skin irritation or sensitization, and a single application of CG‐101 gel imparts skin protection against microbes for significantly longer than conventional 70% ethanol‐based hand sanitizers. These data are the first to indicate that CG‐101 may be a better alternative to alcohol‐based hand sanitizers for long‐term skin protection against infectious diseases.
Improving methanol production by Methylosinus trichosporium through the one factor at a time (OFAT) approach
Authors: Othman Ahmad Razi , Sheng Yap Jun , Kofli Noorhisham Tan , Kamaruddin Siti Kartom 
Published: September 2022

AbstractThe technology of methanol production from the fermentation of methanol‐producing bacteria (methanotroph) is still in the research phase. Maximizing the methanol production through bacteria fermentation in this process is a challenge to researchers. By optimizing the biological process, this technology can potentially fill the demand gap in methanol industries. Methylosinus trichosporium is a methanotroph that is used for the production of methanol in this analysis. Using OD600 analysis, the rate and growth profile for M. trichosporium is determined. The one factor at a time (OFAT) method was chosen to optimize the methanol production (percentage of methane, pH, and phosphate ion), and the optimum condition for this bacterium was determined. M. trichosporium showed a specific growth rate at 0.02 h–1 with the exponential phase reaching the maximum at 90 h of the cultivation period. Optimization analysis showed that the maximum methanol production by this bacterium was at a 1:1 methane–air ratio, a pH of 6.3–6.5, and 40 mM of phosphate ions. The ability of M. trichosporium to produce methanol was proved in this analysis with the maximum rate of production at 0.072 mg L–1 h–1. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.