bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrafast Lithium‐Ion Batteries with Long‐Term Cycling Performance Based on Titanium Carbide/3D Interconnected Porous Carbon
Authors: Chen Dong , Geng Jitao , Sui Yangyang , Jin Zhihua , Qian Wenjing , Zhang Qijian , Aizudin Marliyana , Ang Edison Huixiang , Liu Quan , Geng Hongbo , Rui Xianhong 
Published: February 2022

AbstractCarbon‐based materials are a new class of highly conductive materials that have shown cutting‐edge performance in energy storage. However, the lack of a rational design for three‐dimensional (3D) structures continues to limit its performance in lithium‐ion batteries (LIBs). Herein, we report a 3D layered titanium carbide (TiC) prepared by a facile one‐pot carbonization treatment. This as‐prepared TiC anode has unique continuous 3D architecture, embedded with nanodots and surface oxygenated defects that can provide fast electron and ionic transportation, as well as multiple electrochemical sites for the intercalation/deintercalation of lithium ions in LIBs, resulting in fast rate capability and excellent cycle life of LIBs, for instance, the LIBs consisting of 3D TiC exhibits a specific capacity of 225 mAh g−1 at 10 A g−1 after 10,000 cycles with a capacity retention of 95%. Our findings reinvent carbon‐based materials, specifically TiC, as promising anode materials for LIBs.
Pharmacokinetics and Safety of the Nucleoside Analog Antiviral Drug Galidesivir Administered to Healthy Adult Subjects
Authors: Mathis Amanda , Collins David , Dobo Sylvia , Walling Dennis M. , Sheridan William P. , Taylor Ray 
Published: February 2022

AbstractGalidesivir (BCX4430) is an adenosine nucleoside analog broadly active in cell culture against multiple RNA virus families, and active in animal models of viral diseases associated with Ebola, Marburg, yellow fever, Zika, and Rift Valley fever. Current studies demonstrated the pharmacokinetics and safety of the first‐in‐human evaluations of galidesivir as intramuscular (IM) and intravenous (IV) formulations. Two double‐blind, placebo‐controlled, dose‐ranging studies were conducted enrolling 126 healthy subjects. Study 1 evaluated the safety and tolerability of IM galidesivir over single day dosing, single day dosing ± lidocaine, and 7‐day dosing with lidocaine. Study 2 evaluated the safety and tolerability of single ascending doses of IV galidesivir. Safety and tolerability were evaluated via clinical and laboratory monitoring. The plasma concentration–time profile of galidesivir at doses 0.3 to 10 mg/kg IM was characterized by rapid absorption, an initial rapid distribution and clearance phase, and an extended terminal elimination phase. The initial rapid distribution and extended terminal elimination were mimicked in the profile of galidesivir at doses 5 to 20 mg/kg IV. No fatal events or related serious adverse events were reported. No clinically significant dose‐related trends in laboratory values, vital signs, electrocardiograms, or echocardiograms were noted. Galidesivir was safe and generally well tolerated.
Lack of Electrocardiographic Effects of Deucravacitinib in Healthy Subjects
Authors: Chimalakonda Anjaneya , Singhal Shalabh , Darbenzio Raymond , Dockens Randy , Marchisin David , Banerjee Subhashis , Girgis Ihab G. , Throup John , He Bing , Aras Urvi , Murthy Bindu 
Published: February 2022

AbstractDeucravacitinib is a novel, oral, selective inhibitor of the intracellular signaling kinase tyrosine kinase 2. This phase 1, randomized, partially double‐blind, 4‐period crossover study in healthy adults was conducted to determine whether deucravacitinib 12 mg (therapeutic dose) or 36 mg (supratherapeutic dose) had a clinically relevant effect on the corrected QT interval and other electrocardiographic (ECG) parameters. Subjects received 1 of 4 sequences of placebo, deucravacitinib 12 mg, deucravacitinib 36 mg, and moxifloxacin 400 mg (positive control) in a randomized crossover fashion. The placebo‐corrected change from baseline for the QT interval corrected for heart rate using the Fridericia method (QTcF), ECG parameters, and safety measures were evaluated. A clinically meaningful QTcF prolongation of >10 milliseconds was not found for deucravacitinib at tested doses. Assay sensitivity was demonstrated by the observation of known QT effects of moxifloxacin in the study. Deucravacitinib had no clinically relevant effect on other parameters and was generally well tolerated. The majority of adverse events (AEs) were mild, and all AEs resolved by study's end. Three treatment‐related serious AEs of pharyngitis, cellulitis, and lymphadenopathy occurred in 1 subject following administration of deucravacitinib 12 mg, but resolved by end of study. This study demonstrated that a single oral dose of deucravacitinib 12 or 36 mg did not produce a clinically relevant effect on the corrected QT interval or other measured ECG parameters in healthy adults.
Safety, Pharmacokinetics, and Pharmacodynamics of Oral Insulin Administration in Healthy Subjects: A Randomized, Double‐Blind, Phase 1 Trial
Authors: Zhang Yifei , Zhou Weiwei , Shen Liyun , Lang Liqun , Huang Xing , Sheng Haiyuan , Ning Guang , Wang Weiqing 
Published: February 2022

AbstractOral delivery is an ideal method of insulin administration and is currently a promising research field. Here, we evaluated the safety, pharmacokinetic, and pharmacodynamic characteristics of oral administration of an insulin capsule (ORMD‐0801) with 2 different sources of recombinant human insulin. This was a single‐center, randomized, double‐blind, placebo‐controlled, dose‐escalating phase 1 trial. Single dosing of the oral insulin capsule was administered in 70 healthy Chinese subjects. In stage 1, four dose groups (8, 16, 32, and 48 mg) for capsules containing Sanofi insulin and in stage 2, three dose groups (8, 32, and 48 mg) containing Hefei Tianmai insulin were evaluated consequently. The results showed that the oral insulin formulations with either source in the dose range 8 to 48 mg were safe, and no serious adverse events were observed. After a standard breakfast 45 minutes after dosing, the area under the concentration‐time curve (AUC) from time 0 to time t and AUC from time 0 to infinity for insulin in the 8‐mg and 48‐mg dose groups in stage 1 and for 8‐ to 48‐mg groups in stage 2 were slightly increased compared with placebo, but no significant dose‐related changes in the pharmacokinetic parameters were observed for either stage. The peak‐valley difference and the change in value of the AUC for glucose from baseline showed a dose‐related increase in the dose range from 8 to 48 mg in both stages. Together, this study indicated that in healthy Chinese subjects, this oral capsule containing 2 different insulin formulations was safe and well tolerated after a single‐dose administration.
Effect of Roxadustat on the Pharmacokinetics of Simvastatin, Rosuvastatin, and Atorvastatin in Healthy Subjects: Results From 3 Phase 1, Open‐Label, 1‐Sequence, Crossover Studies
Authors: Groenendaal‐van de Meent Dorien , den Adel Martin , Kerbusch Virginie , van Dijk Jan , Shibata Tomohisa , Kato Kota , Schaddelee Marloes 
Published: February 2022

AbstractRoxadustat inhibits breast cancer resistance protein and organic anion transporting polypeptide 1B1, which can affect coadministered statin concentrations. Three open‐label, 1‐sequence crossover phase 1 studies in healthy subjects were conducted to assess effects from steady‐state 200‐mg roxadustat on pharmacokinetics and tolerability of 40‐mg simvastatin (CL‐0537 and CL‐0541), 40‐mg atorvastatin (CL‐0538), or 10‐mg rosuvastatin (CL‐0537). Statins were dosed concomitantly with roxadustat in 28 (CL‐0537) and 24 (CL‐0538) healthy subjects, resulting in increases of maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from the time of dosing extrapolated to infinity (AUCinf) 1.87‐ and 1.75‐fold for simvastatin, 2.76‐ and 1.85‐fold for simvastatin acid, 4.47‐ and 2.93‐fold for rosuvastatin, and 1.34‐ and 1.96‐fold for atorvastatin, respectively. Additionally, simvastatin dosed 2 hours before, and 4 and 10 hours after roxadustat in 28 (CL‐0541) healthy subjects, resulted in increases of Cmax and AUCinf 2.32‐ to 3.10‐fold and 1.56‐ to 1.74‐fold for simvastatin and 2.34‐ to 5.98‐fold and 1.89‐ to 3.42‐fold for simvastatin acid, respectively. These increases were not attenuated by time‐separated statin dosing. No clinically relevant differences were observed for terminal elimination half‐life. Concomitant 200‐mg roxadustat and a statin was generally well tolerated during the study period. Roxadustat effects on statin Cmax and AUCinf were statin and administration time dependent. When coadministered with roxadustat, statin‐associated adverse reactions and the need for statin dose reduction should be evaluated.
A Phase 1 Clinical Study Evaluating the Effects of Cenobamate on the QT Interval
Authors: Darpo Borje , Sager Philip T. , Xue Hongqi , Kamin Marc 
Published: February 2022

AbstractCenobamate is an antiseizure medication for uncontrolled focal seizures. This thorough QT study assessed the effects of therapeutic and supratherapeutic cenobamate doses (maximum recommended dose, 400 mg/day) on correct QT interval (QTc) in healthy adults (N = 108) randomly assigned to 1 of 3 treatments: (A) cenobamate (days 1‐63) up‐titrated by 50‐mg increments weekly to a 200 mg/day therapeutic dose (day 35) and then by 100 mg weekly to a 500 mg/day supratherapeutic dose (day 63), with placebo‐moxifloxacin (days −1 and 64); (B) moxifloxacin 400 mg (day −1; positive control), placebo‐cenobamate (days 1‐63), and placebo‐moxifloxacin (day 64); and (C) placebo‐moxifloxacin (day −1), placebo‐cenobamate (days 1‐64), and moxifloxacin 400 mg (day 64). The primary end point was baseline‐adjusted, placebo‐corrected QTc (ΔΔQTcF; corrected for heart rate [HR] by Fridericia's method) with cenobamate 200 and 500 mg/day. Baseline electrocardiographic parameters were balanced across groups. Mean ΔΔQTcF was negative throughout for cenobamate doses (largest: day 35, −10.8 milliseconds; day 63, −18.4 milliseconds). Based on concentration‐QTc analysis, ∆∆QTcF effect was predicted as −9.85 and −17.14 milliseconds at mean peak plasma levels of therapeutic (200 mg/day; 23.06 μg/mL) and supratherapeutic (500 mg/day; 63.96 μg/mL) doses. Cenobamate had no clinically relevant prolonging effect on electrocardiographic parameters (eg, PR, QRS); HR effects were similar to placebo. Cenobamate showed slight dose‐related shortening of QTc, but to a degree not known to be clinically relevant (no reductions ≤340 milliseconds). Cenobamate had no clinically relevant effects on HR or electrocardiographic parameters and no QTc‐prolonging effect at therapeutic/supratherapeutic doses. Cenobamate is contraindicated in patients with short‐QT syndrome and caution should be used when coadministering with drugs that shorten QT interval.
Sulfur Dioxide Capture in Metal‐Organic Frameworks, Metal‐Organic Cages, and Porous Organic Cages
Authors: Gupta Nishesh Kumar , López‐Olvera Alfredo , González‐Zamora Eduardo , Martínez‐Ahumada Eva , Ibarra Ilich A. 
Published: February 2022

AbstractCapture, storage and subsequent controlled release or transformation of sulfur dioxide (SO2) in mild conditions is still a challenge in the material science field. Recent advances in the use of porous materials have demonstrated good SO2 capture, particularly in metal‐organic frameworks (MOFs), metal‐organic cages (MOCs), and porous organic cages (POCs). The striking feature of these porous materials is the high SO2 uptake capacity in reversible settings. A partially fluorinated MIL‐101(Cr) is stand‐alone material with the highest SO2 uptake in chemically stable MOFs. Likewise, metal‐free adsorbents like POCs exhibits a reversible SO2 uptake behavior. The SO2 adsorption characteristics of these three structurally and functionally unique adsorbent systems are highly dependent on the binding sites and mode of binding of SO2 molecules. This Review has highlighted the preferential binding sites in these materials to give a full perspective on the field. We anticipate that it will offer valuable information on the progress made towards improving SO2 capture by hybrid systems.
Culture of Cutaneous Leishmania from Skin Biopsy Specimens
Authors: Paun Andrea 
Published: February 2022

AbstractThis protocol describes the culture of Leishmania parasites from skin biopsy samples of patients with cutaneous lesions. The use of antibiotics to prevent bacterial contamination of these cultures increases the ability of researchers to collect isolates for various research purposes, including genetic analysis and in vitro and in vivo experiments. © Published 2022. This article is a U.S. Government work and is in the public domain in the USA.Basic Protocol: Culture of Leishmania from skin biopsy specimens.
Post‐Stroke Hemiplegic Rodent Evaluation: A Framework for Assessing Forelimb Movement Quality Using Kinematics
Authors: Balbinot Gustavo , Bandini Andrea , Schuch Clarissa Pedrini 
Published: February 2022

AbstractKinematics is the gold‐standard method for measuring detailed joint motions. Recent research demonstrates that post‐stroke kinematic analysis in rats reveals reaching abnormalities similar to those seen in humans after stroke. Nonetheless, behavioral neuroscientists have failed to incorporate kinematic methods for assessing movement quality in stroke models. The availability of a user‐friendly method to assess multi‐segment forelimb kinematics models should greatly increase uptake of this approach. Here, we present a framework for multi‐segment forelimb analysis in rodents after stroke. This method greatly enhances the understanding of post‐stroke forelimb motor recovery by including several movement quality metrics often used in human clinical work, such as upper‐limb linear and angular kinematics, movement smoothness and kinetics, abnormal synergies, and compensations. These metrics may constitute a preclinical surrogate for the Fugl‐Meyer assessment of hemiplegic patients. The data obtained using this method are 83 outputs of linear and angular kinematics and kinetics. The outputs also include 24 time series of continuous data, which afford a graphical representation of the kinematics and kinetics of the reaching cycle. We show that post‐stroke rodents displayed many features resembling those seen in humans after stroke that are evident only when multi‐segment kinematics models are considered. This method expands the knowledge derived from methods constrained to paw movements to a multi‐segment forelimb movement quality framework. Moreover, it highlights the need for preclinical work to consider more sensitive measures of sensorimotor impairment and recovery as a means to enhance the interpretation of true recovery and compensation. © 2022 Wiley Periodicals LLC.This article was corrected on 4 August 2022. See the end of the full text for details.Basic Protocol: Recording and data analysis of rodents performing the Montoya staircase task
Partial epithelial–mesenchymal transition during enamel development
Authors: Bazina Fayrouz , Brouxhon Sabine M. , Kyrkanides Stephanos 
Published: February 2022

AbstractObjectivesWe set out to investigate whether a hybrid stem‐like p‐EMT phenotype develops during murine molar enamel development in vivo.Setting and Sample PopulationHistology specimens incorporating molar tooth buds harvested from mice at post‐natal day 4 (P4) were included in our studies.Materials and MethodsWe employed double immunofluorescence staining to analyze the simultaneous expression of the epithelial marker E‐cadherin and the mesenchymal marker N‐cadherin in histology specimens with tooth buds harvested from P4 mice. Moreover, we evaluated the expression of the core master stem cell markers Oct4 and Sox2, as well as the mature ameloblast marker amelogenin.ResultsHere we document the co‐expression of E‐cadherin and N‐cadherin in a sub‐population of pre‐ameloblasts in the inner enamel epithelium suggestive of the presence of a hybrid epithelial/mesenchymal phenotype resulting from p‐EMT. Moreover, the core stem cell factors Oct4 and Sox2 colocalized with E‐cadherin expressing pre‐ameloblasts, whereas the mesenchymal marker N‐cadherin was expressed specifically by amelogenin–positive mature secretory ameloblasts.ConclusionsThe differentiation of E‐cadherin–positive pre‐ameloblasts towards N‐cadherin–positive mature secretory ameloblasts transition through a previously unidentified epithelial/mesenchymal stage derived through p‐EMT, co‐expressing the master transcription factors Oct4 and Sox2.
Channel‐lobe transition zone development in tectonically active settings: Implications for hybrid bed development
Authors: Brooks Hannah L. , Ito Makoto , Zuchuat Valentin , Peakall Jeff , Hodgson David M. 
Published: February 2022

AbstractChannel‐lobe transition zones are dynamic areas located between deepwater channels and lobes. Presented here is a rare example of an exhumed channel‐lobe transition zone from an active‐margin setting, in the Kazusa forearc Basin, Boso Peninsula, Japan. This Plio‐Pleistocene outcrop exposes a thick (tens of metres) channel‐lobe transition zone succession with excellent dating control, in contrast to existing poorly dated studies of thinner (metres) deposits in tectonically quiescent settings. This high‐resolution outcrop permits the roles of climate and associated relative sea‐level changes on stratigraphic architecture to be assessed. Three development stages are recognised with an overall coarsening‐upward then fining‐upwards trend. Each stage is interpreted to record one obliquity‐driven glacioeustatic sea‐level fall‐then‐rise cycle, based on comparison with published data. Deposition of the thickest and coarsest strata, Stage 2, is interpreted to record the end of a period of relative sea‐level fall. The thinner and finer strata of Stages 1 and 3 formed during interglacial periods where the stronger Kuroshio Oceanic Current, coupled to increased monsoonally driven tropical cyclone frequency and intensity, likely resulted in inhibited downslope sediment transfer. A key aspect of channel‐lobe transition zone deposits in this case is the presence of a diverse range of hybrid beds, in contrast to previous work where they have primarily been associated with lobe fringes. Here hybrid bed characteristics, and grain‐size variations, are used to assess the relative importance of longitudinal and vertical segregation processes, and compared to existing models. Compared to channel‐lobe transition zones in tectonically quiescent basin‐fills, this channel‐lobe transition zone shows less evidence of bypassing flows (i.e. thicker stratigraphy, more isolated scour‐fills, fewer bypass lags) and has significantly more hybrid beds. These features may be common in active basin channel‐lobe transition zones due to: high subsidence rates; high sedimentation rates; and disequilibrium of tectonically active slopes. This disequilibrium could rejuvenate erodible mud‐rich substrate, leading to mud‐rich flows arriving at the channel‐lobe transition zone, and decelerating rapidly, forming hybrid beds.
Effects of temperature and oxygen on cyanobacterial DNA preservation in sediments: A comparison study of major taxa
Authors: Mejbel Hebah S. , Dodsworth William , Pick Frances R. 
Published: February 2022

AbstractThe analysis of sediment DNA has emerged as a promising alternative to classical paleolimnological proxies, which typically rely on hard fossils to reconstruct environmental change. In recent studies, the timing and causes of apparent increases in toxic cyanobacterial blooms in lakes around the world have been identified by high‐throughput sequencing of cyanobacterial 16S rRNA genes from decadal‐ and centennial‐scale sediment records. However, the reconstruction of ecological time series can be influenced by DNA degradation processes interfering with taxonomic resolution and quantification of target genes. To determine whether some cyanobacterial taxa degrade more rapidly than others, a one‐year incubation experiment was performed to estimate degradation rates in sediments under contrasting environmental conditions of temperature (4°C vs. 25°C) and sediment redox (oxic vs. anoxic). Using sediments collected from an oligotrophic lake, serum bottles were inoculated with either Microcystis aeruginosa, Synechococcus sp., or Trichormus variabilis. These cyanobacteria were chosen because they are widespread yet exhibit contrasting morphologies. The absolute concentrations of the target genes were measured over time through droplet digital PCR. The three taxa exhibited log‐linear declines with different rates of decay. Based on first‐order linear decay models, Microcystis exhibited faster decay under oxic conditions, whereas Synechococcus sp. and Trichormus were both temperature and anoxic dependent. Overall, cyanobacterial decay rates were lowest under 4°C anoxic conditions, corresponding to conditions in deep temperate lakes. Under 4°C, Synechococcus exhibited the lowest degradation rates followed by Trichormus, then Microcystis. These findings will be useful in the interpretation of population and community structure data based on sediment DNA and advances our current understanding of cyanobacterial preservation in sediment.
Prevalence and prognostic impact of cognitive frailty in elderly patients with heart failure: sub‐analysis of FRAGILE‐HF
Authors: Yamamoto Shuhei , Yamasaki Saeko , Higuchi Satoko , Kamiya Kentaro , Saito Hiroshi , Saito Kazuya , Ogasahara Yuki , Maekawa Emi , Konishi Masaaki , Kitai Takeshi , Iwata Kentaro , Jujo Kentaro , Wada Hiroshi , Kasai Takatoshi , Nagamatsu Hirofumi , Ozawa Tetsuya , Izawa Katsuya , Aizawa Naoki , Makino Akihiro , Oka Kazuhiro , Momomura Shin‐ichi , Kagiyama Nobuyuki , Matsue Yuya 
Published: February 2022

AbstractAimsAlthough evidence suggests that cognitive decline and physical frailty in elderly patients with heart failure (HF) are associated with prognosis, the impact of concurrent physical frailty and cognitive impairment, that is, cognitive frailty, on prognosis has yet to be fully investigated. The current study sought to investigate the prevalence and prognostic impact of cognitive frailty in elderly patients with HF.Methods and resultsThis study is a sub‐analysis of FRAGILE‐HF, a prospective multicentre observational study involving patients aged ≥65 years hospitalized for HF. The Fried criteria and Mini‐Cog were used to diagnose physical frailty and cognitive impairment, respectively. The association between cognitive frailty and the combined endpoint of mortality and HF rehospitalization within 1 year was then evaluated. Among the 1332 patients identified, 1215 who could be assessed using Mini‐Cog and the Fried criteria were included in this study. Among those included, 279 patients (23.0%) had cognitive frailty. During the follow‐up 1 year after discharge, 398 combined events were observed. Moreover, cognitive frailty was determined to be associated with a higher incidence of combined events (log‐rank: P = 0.0146). This association was retained even after adjusting for other prognostic factors (hazard ratio: 1.55, 95% confidence interval: 1.13–2.13). Furthermore, a sensitivity analysis using grip strength, short physical performance battery, and gait speed to determine physical frailty instead of the Fried criteria showed similar results.ConclusionsThis cohort study found that 23% of elderly patients with HF had cognitive frailty, which was associated with a 1.55‐fold greater risk for combined events within 1 year compared with patients without cognitive frailty.