bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Vascular Disrupting Agents Noncovalent Polymeric Nanomedicine: Significantly Increased Antitumor Therapeutic Efficiency
Authors: Lv Jianlin , Xu Yajun , Huang Yue , Yu Haiyang , Tang Zhaohui 
Published: March 2022

Comprehensive SummaryPlinabulin, a potential vascular disrupting agent (VDA), has entered the phase III clinical trial. However, the antitumor efficacy of Plinabulin is only moderate, which is probably because of the short action time of acting on tubulin. To maintain a constant VDAs concentration around the tumor vascular endothelial cells, in this study, we developed a novel Plinabulin derivate named HBP and further prepared noncovalent HBP nanoparticles (HBP NPs). We examined and compared the antitumor efficiency of HBP and HBP NPs in 4T1 tumor‐bearing mice. HBP NPs significantly increased therapeutic efficiency than HBP, even with a quarter dose. These findings exhibited in this paper further confirmed the opinion that VDAs nanomedicine could markedly enhance tumor therapeutic effect more than small molecular VDAs.
Brightness, lightness, colorfulness, and chroma in CIECAM02 and CAM16
Authors: Hellwig Luke , Fairchild Mark D. 
Published: March 2022

AbstractIn the CIECAM02 and CAM16 color appearance models, brightness is computed as a nonlinear function of lightness. This paper traces the history of that nonlinearity to its roots in the Hunt color appearance model. A new, more robust, linear relationship between lightness and brightness is proposed. This new formula also prompts the reevaluation of the CAM16 equations for chroma, colorfulness, and saturation. The new formulas for these perceptual attributes are tested on experimental data from the Munsell color order system and the LUTCHI color appearance dataset and are compared to the performance of the original CAM16 equations.
Re‐evaluating the actin‐dependence of spectraplakin functions during axon growth and maintenance
Authors: Qu Yue , Alves‐Silva Juliana , Gupta Kriti , Hahn Ines , Parkin Jill , Sánchez‐Soriano Natalia , Prokop Andreas 
Published: March 2022

AbstractAxons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require loose microtubule bundles that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtubules are the spectraplakins, a well‐conserved family of cytoskeletal cross‐linkers that underlie neuropathies in mouse and humans. Spectraplakin deficiency in mouse or Drosophila causes severe decay of microtubule bundles and reduced axon growth. The underlying mechanisms are best understood for Drosophila’s spectraplakin Short stop (Shot) and believed to involve cytoskeletal cross‐linkage: Shot's binding to microtubules and Eb1 via its C‐terminus has been thoroughly investigated, whereas its F‐actin interaction via N‐terminal calponin homology (CH) domains is little understood. Here, we have gained new understanding by showing that the F‐actin interaction must be finely balanced: altering the properties of F‐actin networks or deleting/exchanging Shot's CH domains induces changes in Shot function—with a Lifeact‐containing Shot variant causing remarkable remodeling of neuronal microtubules. In addition to actin‐microtubule (MT) cross‐linkage, we find strong indications that Shot executes redundant MT bundle‐promoting roles that are F‐actin‐independent. We argue that these likely involve the neuronal Shot‐PH isoform, which is characterized by a large, unexplored central plakin repeat region (PRR) similarly existing also in mammalian spectraplakins.
Urinary clearance of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol: A detailed pharmacokinetic analysis
Authors: Sempio Cristina , Huestis Marilyn A. , Kaplan Bruce , Klawitter Jost , Christians Uwe , Henthorn Thomas K. 
Published: March 2022

AbstractUrine is a common matrix for screening for cannabis use. Urine assays typically measure total 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THCCOOH) concentrations after hydrolysis cleaves the glucuronide. Urine THCCOOH concentration is adjusted by urine creatinine concentration or specific gravity, to account for variable hydration states. Therefore, we performed a population pharmacokinetic analysis of the urinary THCCOOH excretion, urinary flow rate, and creatinine excretion rate data. Urine was obtained over 168 h from six subjects who smoked low‐ (15.8 mg) and high‐dose (33.8 mg) Δ9‐tetrahydrocannabinol (THC) cigarettes on two occasions. Samples were analyzed for THCCOOH concentration by gas chromatography–mass spectrometry (GC‐MS) and volume, time, and creatinine concentration measured. A population pharmacokinetic model of the urinary clearance of THCCOOH was created from these data, and potential covariates of urine creatinine concentration and urine creatinine excretion rate were assessed. Elimination clearance of THCCOOH was estimated as 0.104 ± 0.088 L/min, and its urinary clearance was 0.0022 ± 0.0015 L/min. Total urine excretion of THCCOOH was estimated at 2.3%. Urine flow rate and urine creatinine concentrations were significantly correlated, r2 = 0.35. Creatinine excretion rate was 129.6 ± 71.0 ml/min, and the intrasubject variability was 31%–52% (SD%) during the week. Urinary creatinine excretion rate was a significant covariate for the urinary clearance of THCCOOH. Creatinine clearance is a significant covariate for urinary THCCOOH clearance. Only 2%–3% of bioavailable THC is excreted as THCCOOH and THCCOO‐glucuronide via the urine. Correction of urine drug and/or metabolite concentration with urine creatinine concentration or specific gravity may be more problematic than previously appreciated.
Flowering time advances since the 1970s in a sagebrush steppe community: Implications for management and restoration
Authors: Bloom Trevor D. S. , O'Leary Donal S. , Riginos Corinna 
Published: March 2022

AbstractClimate change is widely known to affect plant phenology, but little is known about how these impacts manifest in the widespread sagebrush ecosystem of the Western United States, which supports a number of wildlife species of concern. Shifts in plant phenology can trigger consequences for the plants themselves as well as the communities of consumers that depend upon them. We assembled historical observations of first‐flowering dates for 51 species collected in the 1970s and 1980s in a montane sagebrush community in the Greater Yellowstone Ecosystem and compared these to contemporary phenological observations targeting the same species and locations (2016–2019). We also assembled regional climate data (average spring temperature, day of spring snowmelt, and growing degree days) and tested the relationship between first‐flowering time and these variables for each species. We observed the largest change in phenology in early‐spring flowers, which, as a group, bloomed on average 17 days earlier, and as much as 36 days earlier, in the contemporary data set. Mid‐summer flowers bloomed on average 10 days earlier, nonnative species 15 days earlier, and berry‐producing shrubs 5 days earlier, while late summer flowering plants did not shift. The greatest correlates of early‐spring and mid‐summer flowering were average spring temperature and day of snowmelt, which was 21 days earlier, on average, in 2016–2019 relative to the 1973–1978 observations. The shifts in flowering phenology that we observed could indicate developing asynchronies or novel synchronies of these plant resources and wildlife species of conservation concern, including Greater Sage‐grouse, whose nesting success is tied to availability of spring forbs; grizzly bears, which rely heavily on berries for their fall diet; and pollinators. This underscores the importance of maintaining a diverse portfolio of native plants in terms of species composition, genetics, phenological responsiveness to climatic cues, and ecological importance to key wildlife and pollinator species. Redundancy within ecological niches may also be important considering that species roles in the community may shift as climate change affects them differently. These considerations are particularly relevant to restoration and habitat‐enhancement projects in sagebrush communities across western North America.
Responder analysis for improvement in 6‐min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency
Authors: Anker Stefan D. , Ponikowski Piotr , Khan Muhammad Shahzeb , Friede Tim , Jankowska Ewa A. , Fabien Vincent , Goehring Udo‐Michael , Metra Marco , Piña Ileana L. , Coats Andrew J.S. , Rosano Giuseppe , Dorigotti Fabio , Comin‐Colet Josep , Van Veldhuisen Dirk J. , Filippatos Gerasimos S. , Butler Javed 
Published: March 2022

AimImproving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR‐HF and CONFIRM‐HF assessed the likelihood of improvement or deterioration in 6‐min walk test (6MWT) among iron‐deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).Methods and resultsData for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6–37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57–2.96]; p < 0.0001), ≥30 m (2.00 [1.44–2.78]; p < 0.0001), and ≥40 m (2.29 [1.60–3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38–0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24.ConclusionFerric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron‐deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.
Recent advances and prospects in purification and heterologous expression of lactoferrin
Authors: Cui Shixiu , Lv Xueqin , Sun Guoyun , Wu Wenyang , Xu Hong , Li Yuelong , Liu Yanfeng , Li Jianghua , Du Guocheng , Wang Miao , Liu Long 
Published: March 2022

AbstractLactoferrin is an 80 kDa iron‐binding glycoprotein of the transferrin family, which is abundant in milk and in most biological fluids. Besides the direct antimicrobial properties, lactoferrin can regulate immune responses and prevent infection and septic shock. Membrane adsorption and chromatographic methods are usually used for separating and purifying of lactoferrin from bovine milk. However, the content of lactoferrin in milk is relatively low, resulting in a high cost of producing lactoferrin. Meanwhile, as a heterologous protein applied to the human body, it may cause a certain antigen response. Therefore, obtaining a large amount of biologically active lactoferrin has always been a research hot topic. This review first introduced the physical and chemical properties, and biological activities of lactoferrin. Then, the current recombinant expression systems for lactoferrin were summarized. Finally, the current challenges and the future development trends of efficient synthesis of lactoferrin were discussed.
Recovery of superior frontal gyrus cortical thickness and resting‐state functional connectivity in abstinent heroin users after 8 months of follow‐up
Authors: Yang Wenhan , Zhang Min , Tang Fei , Du Yanyao , Fan Li , Luo Jing , Yan Cui , Wang Shicong , Zhang Jun , Yuan Kai , Liu Jun 
Published: March 2022

AbstractCompared with healthy controls, heroin users (HUs) show evidence of structural and functional brain alterations. However, little is known about the possibility of brain recovery after protracted heroin abstinence. The purpose of this study was to investigate whether brain recovery is possible after protracted abstinence in HUs. A total of 108 subjects with heroin addiction completed structural and functional scans, and 61 of those subjects completed 8‐month follow‐up scans. Resting‐state data and 3D‐T1 MR images were collected for all participants, first at baseline and again after 8 months. Cognitive function and craving were measured by the Trail Making Test‐A (TMT‐A) and Visual Analog Scale for Craving, respectively. The cortical thickness and resting‐state functional connectivity (RSFC) differences were then analyzed and compared between baseline and follow‐up, and correlations were obtained between neuroimaging and behavioral changes. HUs demonstrated improved cognition (shorter TMT‐A time) and reduced craving at the follow‐up (HU2) relative to baseline (HU1), and the cortical thickness in the bilateral superior frontal gyrus (SFG) was significantly greater at HU2 than at HU1. Additionally, the RSFC of the left SFG with the inferior frontal gyrus (IFG), insula, and nucleus accumbens and that of the right SFG with the IFG, insula and orbitofrontal cortex (OFC) were increased at HU2. The changes in TMT‐A time were negatively correlated with the RSFC changes between the left SFG and the bilateral IFG, the bilateral caudate, and the right insula. The changes in craving were negatively correlated with the RSFC changes between the left OFC and the bilateral SFG. Our results demonstrated that impaired frontal‐limbic neurocircuitry can be partially restored, which might enable improved cognition as well as reduced craving in substance‐abusing individuals. We provided novel scientific evidence for the partial recovery of brain circuits implicated in cognition and craving after protracted abstinence.
The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics
Authors: Elibol Birsen , Severcan Mete , Jakubowska‐Dogru Ewa , Dursun Ilknur , Severcan Feride 
Published: March 2022

AbstractThe structural effects of vitamin A‐deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT‐IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3‐months. The rats were decapitated at different ethanol withdrawal times and FT‐IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insignificant structural effects on lipids. In vitamin A deficiency, ethanol produced structural changes in lipids by lipid ordering especially in the early‐ethanol withdrawal. Furthermore, an increase in lipid and protein content, saturated/unsaturated lipid ratio, a decrease in nucleic acids content and decrease in membrane fluidity were observed. These changes were less severe in the presence of Vitamin A. This study is clinically important for individuals with vitamin A deficiency because they have to be more cautious when consuming alcohol to protect themselves from cognitive dysfunctions.
Noises investigations and image denoising in femtosecond stimulated Raman scattering microscopy
Authors: Ranjan Rajeev , Costa Giovanni , Ferrara Maria Antonietta , Sansone Mario , Sirleto Luigi 
Published: March 2022

AbstractIn the literature of SRS microscopy, the hardware characterization usually remains separate from the image processing. In this article, we consider both these aspects and statistical properties analysis of image noise, which plays the vital role of joining links between them. Firstly, we perform hardware characterization by systematic measurements of noise sources, demonstrating that our in‐house built microscope is shot noise limited. Secondly, we analyze the statistical properties of the overall image noise, and we prove that the noise distribution can be dependent on image direction, whose origin is the use of a lock‐in time constant longer than pixel dwell time. Finally, we compare the performances of two widespread general algorithms, that is, singular value decomposition and discrete wavelet transform, with a method, that is, singular spectrum analysis (SSA), which has been adapted for stimulated Raman scattering images. In order to validate our algorithms, in our investigations lipids droplets have been used and we demonstrate that the adapted SSA method provides an improvement in image denoising.
Comparing direct oral anticoagulants and vitamin K antagonist use in morbidly obese patients with venous thromboembolism: A single center retrospective cohort study
Authors: Scott Lia C. , Li Juan , Cafuir Lorraine A. , Gaddh Manila , Kempton Christine L 
Published: March 2022

AbstractIntroduction: Limited data exists on the safety and efficacy of direct‐acting oral anticoagulants (DOAC) use in morbidly obese patients with venous thromboembolism (VTE). Given the benefits of DOAC use over vitamin K antagonists (VKAs), in terms of monitoring requirements, and dietary and drug interactions, it is important to evaluate whether this is consistent in the higher risk for VTE recurrence morbidly obese group body mass index (BMI ≥ 40 kg/m2).Materials and methods: This retrospective, single‐center cohort study included patients with a BMI of at least 40 kg/m2 who were admitted to Emory University Hospital from 1st January 2012 to 31st May 2020 with acute VTE, and subsequently initiated on anticoagulation treatment with either DOAC or VKA (warfarin). Univariate and bivariate analyses were used to evaluate differences in demographics by treatment type and BMI. Multivariate Cox proportional hazard regression was used to assess the risk of VTE recurrence by type of treatment among morbidly obese patient subgroup.Results: There were 247 (11.8%) morbidly obese (≥ 40 kg/m2) patients who were more likely than non‐obese patients to be younger, female, and of non‐white race. Thirty percent of the study population (n=74) had a BMI >50 kg/m2. T ime‐to‐event analysis confirmed that the hazard of experiencing a recurrent thrombosis was not statistically significantly different among morbidly obese patients treated with a DOAC compared with VKA (hazard ratio [HR]: 0.28, confidence interval [CI] 0.07‐1.11, p = 0.07).Conclusions: This study aligns with previous literature and confirms that morbidly obese patients receiving DOAC or VKA have similar risks of recurrent VTE.
Quinolinecarbonitrile: Solvent‐free one‐pot synthesis, in vitro studies against leukemia cell lines, molecular docking, and potential Mcl‐1 inhibitors
Authors: Selim Yasser , Fadda Ahmed A. , Tawfik Eman H. , Abd El‐Azim Mohamed H. M. 
Published: March 2022

AbstractIn our study, we present an environmentally benign procedure for green synthesis of 4‐aryl/hetero aryl benzo[h]quinolin‐2‐one‐3‐carbonitrile. The synthesis protocol of quinolone carbonitrile derivatives, including the reaction of tetralone 1 and ethyl cyano acetate with hetero aryl and ammonium acetate under solvent‐free conditions, compounds 4a–i, 5, and 6, were obtained and its chemical structure was proved by different spectroscopic methods. The present synthetic approach could effectively produce different quinolone carbonitrile derivatives with high yields in the absence of solvent and in short reaction time, making it a green and sustainable process. All new compounds were screened for cytotoxicity on two kinds of acute lymphoblastic leukemia (ALL) cells, CRL‐2898, and MOLT‐4, and compared with normal human primary peripheral blood mononuclear cells PCS‐800‐011 using MTT assay. Compound 4g showed potent cytotoxicity with IC50 value 9.81, 9.81 μM against CRL‐2898 and MOLT‐4, respectively, without effect on normal cell. The most cytotoxic compounds 4g, 5, and 6 were docked into the active site of myeloid cell leukemia‐1(Mcl‐1). Compounds 4g and 6 showed strong hydrogen bond interaction with Arg263 through their carbonyl groups, achieving a binding mode similar to that of the native ligand.
Atmospheric circulation patterns that trigger heavy rainfall in West Africa
Authors: Bliefernicht Jan , Rauch Manuel , Laux Patrick , Kunstmann Harald 
Published: March 2022

AbstractClassification of atmospheric circulation patterns (CP) is a common tool for downscaling rainfall, but it is rarely used for West Africa. In this study, a two‐step classification procedure is proposed for this region, which is applied from 1989 to 2010 for the Sudan‐Sahel zone (Central Burkina Faso) with a focus on heavy rainfall. The approach is based on a classification of large‐scale atmospheric CPs (e.g., Saharan Heat Low) of the West African Monsoon using a fuzzy rule‐based method to describe the seasonal rainfall variability. The wettest CPs are further classified using meso‐scale monsoon patterns to better describe the daily rainfall variability during the monsoon period. A comprehensive predictor screening for the seasonal classification indicates that the best performing predictor variables (e.g., surface pressure, meridional moisture fluxes) are closely related to the main processes of the West African Monsoon. In the second classification step, the stream function at 700 hPa for identifying troughs and ridges of tropical waves shows the highest performance, providing an added value to the overall performance of the classification. Thus, the new approach can better distinguish between dry and wet CPs during the rainy season. Moreover, CPs are identified that are of high relevance for daily heavy rainfall in the study area. The two wettest CPs caused roughly half of the extremes on about 6.5% of days. Both wettest patterns are characterized by an intensified Saharan Heat Low and a cyclonic rotation near the study area, indicating a tropical wave trough. Since the classification can be used to condition other statistical approaches used in climate sciences and other disciplines, the presented classification approach opens many different applications for the West African Monsoon region.