bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure‐Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results From Phase II and Phase III Induction and Maintenance Studies
Authors: Mukherjee Arnab , Tsuchiwata Shinichi , Nicholas Timothy , Cook Jack A. , Modesto Irene , Su Chinyu , D’Haens Geert R. , Sandborn William J. 
Published: April 2022

Tofacitinib is an oral small molecule JAK inhibitor for the treatment of ulcerative colitis. Relationships between plasma tofacitinib concentration and efficacy were characterized using exposure‐response (E‐R) models, with demographic and disease covariates evaluated as potential predictors of efficacy. Data were from phase II and III (OCTAVE Induction 1 and 2) induction studies, and a phase III maintenance study (OCTAVE Sustain). Induction studies included 1,355 patients (tofacitinib 0.5, 3, 10, or 15 mg b.i.d. or placebo). The maintenance study included 592 patients (tofacitinib 5 or 10 mg b.i.d. or placebo). E‐R models, including induction patients predicted placebo‐adjusted remission rates of 6.4% and 12.7% at week 8 for tofacitinib 5 and 10 mg b.i.d., respectively; corresponding rates in patients without prior tumor necrosis factor inhibitor (TNFi) failure were 12.8% and 20.4%. Estimates to achieve/maintain remission at week 52 of maintenance were 29% and 18% (tofacitinib 5 mg b.i.d.), and 41% and 26% (tofacitinib 10 mg b.i.d.), for patients in remission or not following induction, respectively. During maintenance, patients with prior TNFi failure had lower probability of remission on 5 mg b.i.d. (24.9%) than 10 mg b.i.d. (35.0%). Results indicated tofacitinib 10 mg b.i.d. was an appropriate induction dose but suggested efficacy with 5 mg b.i.d. in patients without prior TNFi failure. Tofacitinib 5 mg b.i.d. was efficacious for maintenance, although patients with prior TNFi failure might see additional benefit on 10 mg b.i.d. Per product labeling, recommended tofacitinib induction dose is 10 mg b.i.d., then maintenance at 5 mg b.i.d. For patients who lose response during maintenance, 10 mg b.i.d. may be considered, limited to the shortest duration.Clinicaltrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01458574.
Quantifying the Probing and Selection of Microenvironmental Pores by Motile Immune Cells
Authors: Kroll Janina , Ruiz‐Fernandez Mauricio J. A. , Braun Malte B. , Merrin Jack , Renkawitz Jörg 
Published: April 2022

AbstractImmune cells are constantly on the move through multicellular organisms to explore and respond to pathogens and other harmful insults. While moving, immune cells efficiently traverse microenvironments composed of tissue cells and extracellular fibers, which together form complex environments of various porosity, stiffness, topography, and chemical composition. In this protocol we describe experimental procedures to investigate immune cell migration through microenvironments of heterogeneous porosity. In particular, we describe micro‐channels, micro‐pillars, and collagen networks as cell migration paths with alternative pore size choices. Employing micro‐channels or micro‐pillars that divide at junctions into alternative paths with initially differentially sized pores allows us to precisely (1) measure the cellular translocation time through these porous path junctions, (2) quantify the cellular preference for individual pore sizes, and (3) image cellular components like the nucleus and the cytoskeleton. This reductionistic experimental setup thus can elucidate how immune cells perform decisions in complex microenvironments of various porosity like the interstitium. The setup further allows investigation of the underlying forces of cellular squeezing and the consequences of cellular deformation on the integrity of the cell and its organelles. As a complementary approach that does not require any micro‐engineering expertise, we describe the usage of three‐dimensional collagen networks with different pore sizes. Whereas we here focus on dendritic cells as a model for motile immune cells, the described protocols are versatile as they are also applicable for other immune cell types like neutrophils and non‐immune cell types such as mesenchymal and cancer cells. In summary, we here describe protocols to identify the mechanisms and principles of cellular probing, decision making, and squeezing during cellular movement through microenvironments of heterogeneous porosity. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Immune cell migration in micro‐channels and micro‐pillars with defined pore sizesSupport Protocol 1: Epoxy replica of generated and/or published micro‐structuresSupport Protocol 2: Dendritic cell differentiationBasic Protocol 2: Immune cell migration in 3D collagen networks of variable pore sizes
Differentiation of Human Induced Pluripotent Stem Cells into Keratinocytes
Authors: Koch Peter J. , Webb Saiphone , Gugger Jessica A. , Salois Maddison N. , Koster Maranke I. 
Published: April 2022

AbstractInvestigating basic biological mechanisms underlying human diseases relies on the availability of sufficient quantities of patient cells. As most primary somatic cells have a limited lifespan, obtaining sufficient material for biological studies has been a challenge. The development of induced pluripotent stem cell (iPSC) technology has been a game changer, especially in the field of rare genetic disorders. iPSC are essentially immortal, can be stored indefinitely, and can thus be used to generate defined somatic cells in unlimited quantities. Further, the availability of genome editing technologies, such as CRISPR/CAS, has provided us with the opportunity to create “designer” iPSC lines with defined genetic characteristics. A major advancement in biological research stems from the development of methods to direct iPSC differentiation into defined cell types. In this article, we provide the basic protocol for the generation of human iPSC‐derived keratinocytes (iPSC‐K). These cells have the characteristics of basal epidermal keratinocytes and represent a tool for the investigation of normal epidermal biology, as well as genetic and acquired skin disorders. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Directed differentiation of human iPSC into keratinocytesSupport Protocol 1: Coating cell culture dishes or plates with Vitronectin XF™Support Protocol 2: Freezing iPSCSupport Protocol 3: Preparing AggreWell™400 6‐well plates for EB formationSupport Protocol 4: Coating cell culture dishes or plates with Collagen IVSupport Protocol 5: Immunofluorescence staining of cells
In Vivo Assessment of Ferroptosis and Ferroptotic Stress in Mice
Authors: Ide Kana , Souma Tomokazu 
Published: April 2022

AbstractFerroptosis is iron‐dependent, lipid peroxidation–driven, regulated cell death that is triggered when cellular glutathione peroxidase 4 (GPX4)‐mediated cellular defense is insufficient to prevent pathologic accumulation of toxic lipid peroxides. Ferroptosis is implicated in various human pathologies, including neurodegeneration, chemotherapy‐resistant cancers, ischemia‐reperfusion injury, and acute and chronic kidney diseases. Despite the fact that the ferroptotic process has been rigorously interrogated in multiple preclinical models, the lack of specific and readily available biomarkers to detect ferroptosis in vivo in mouse models makes it challenging to delineate its contribution to key pathologic events in vivo. Critical steps to practically evaluate ferroptosis include, but are not limited to, detecting increased cell death and pathologic accumulation of toxic lipid peroxides and testing augmentation of observed pathologic events by genetic inhibition of the glutathione‐GPX4 axis or mitigation of the pathologic process by ferroptosis inhibitors. Here, we describe methods to evaluate these key features of the ferroptotic process in mice in vivo. Specifically, we describe methods to detect toxic lipid peroxides (4‐hydroxynonenal) and cell death (based on terminal deoxynucleotidyl transferase dUTP nick end labeling staining) as well as a protocol to pharmacologically inhibit ferroptotic stress using liproxstatin‐1. These protocols provide tools for understanding the ferroptotic process in mouse genetic or disease models. © 2022 Wiley Periodicals LLC.Basic Protocol 1: How to use liproxstatin‐1Basic Protocol 2: How to evaluate ferroptosis in mouse kidneys
Bound states of the hydrogen atom in high‐density plasmas
Authors: Shalenov Erik O. , Nuraly Askhat T. , Dzhumagulova Karlygash N. 
Published: April 2022

AbstractIn this work, the interaction potential of dense plasma particles, which takes into account the effect of quantum non‐locality as well as electronic correlations, was used to solve the Schrödinger equation for the hydrogen atom. Energies of bound states were calculated. The results obtained are in good agreement with the results of other authors.
Endoscopic ultrasound‐guided fine‐needle biopsy for the diagnosis of gastric metastasis from breast cancer mimicking primary linitis plastica: A case report
Authors: Yamada Kenta , Kaneko Junichi , Watahiki Moeka , Ida Yuya , Koda Megumu , Fukita Kyoichi , Takeshita Yu , Takahashi Kenichi , Takinami Masaki , Tsuji Atsushi , Nishino Masafumi , Takahashi Yurimi , Sasada Yuzo , Yamada Takanori 
Published: April 2022

AbstractFor gastric lesions in a patient with a history of breast cancer, it is essential to distinguish between primary gastric cancer and gastric metastasis from breast cancer. However, gastric metastasis from breast cancer often mimics primary linitis plastica, and histological diagnosis may be difficult with conventional endoscopic biopsies. Herein, we describe the case of a 75‐year‐old woman who presented at our hospital with epigastralgia and vomiting. She had a history of mastectomy for carcinoma of the right breast and had received hormone therapy as adjuvant therapy. Computed tomography at arrival showed thickening of the gastric wall at the antrum and peritoneal dissemination. Esophagogastroduodenoscopy showed mucosal swelling of the antrum and stenosis of the pylorus, and histological diagnosis failed with conventional endoscopic biopsies. Endoscopic ultrasound‐guided fine‐needle biopsy using a Franseen needle was performed, and a diagnosis of gastric metastasis from breast cancer was made. She received hormone therapy and chemotherapy after deployment of a metallic stent for gastric outlet obstruction. To the best of our knowledge, this is the first case of gastric metastasis from breast cancer diagnosed using endoscopic ultrasound‐guided fine‐needle biopsy.
A Stable and Photoreactive Copper‐Iodide Cubane Suitable for Direct Post‐Functionalization
Authors: Bissessar Damien , Egly Julien , Achard Thierry , Steffanut Pascal , Mauro Matteo , Bellemin‐Laponnaz Stéphane 
Published: April 2022

AbstractTetranuclear copper‐iodide cluster consisting of a {Cu4I4} cubane and diphenylphosphine ligand has been found as a highly stable precursor for further post‐functionalization through hydrophosphination reaction. UV irradiation of the cluster in the presence of various alkenes allows direct functionalization of the latter, giving access to a wide range of copper cubane complexes, a source of molecular diversity for luminescent materials. Such a strategy provided access to the first example of water‐soluble luminescent cubane copper iodide.
Au(I) Fluorido Phosphine Complexes: Tools for the Hydrofluorination of Alkynes
Authors: Rachor Simon G. , Jaeger Ruben , Braun Thomas 
Published: April 2022

AbstractThe reactivity of the Au(I) fluorido complex [Au(F)(SPhos)] (SPhos=dicyclohexyl(2’,6’‐dimethoxy[1,1’‐biphenyl]‐2‐yl)phosphine) (1) towards several alkynes was studied. The formation of fluorovinyl species by formal insertion of the alkyne in the metal‐fluorine bond was observed. Addition of HCl to vinyl complexes resulted in protodeauration and elimination of the hydrofluorinated alkynes. Treatment of1with the terminal alkyne 1‐hexyne resulted in clean formation of the alkynyl complex [Au(C≡CC4H9)(SPhos)] (15), whereas with an excess alkyne hydrofluorination was also observed. Various Au(I) phosphine complexes including1were then compared in their ability to catalyze hydrofluorination reactions of 1‐phenyl‐1‐propyne with Et3N ⋅ 3HF as HF source. Model reactions suggested a reaction mechanism, which imparts a pre‐coordination of an alkyne to a cationic gold center followed by nucleophilic addition of a fluoride. Mechanistic investigations included reactivity studies at [Au(SPhos)][B(C6F5)4)] (17), which was treated with 4‐phenyl‐3‐butyn‐2‐one and TMAF (TMAF=tetramethylammonium fluoride). The reaction led to the formation of the complex [Au(CH3C(O)C=C(F)Ph)(SPhos)] (13), but not the fluorido complex1.
Synthesis of Geminal Bis‐ and Tetrakisphosphonate Ester Derivatives and Their Coordination Behavior Towards Ca(II) Ions
Authors: Koehne Ingo , Pietschnig Rudolf 
Published: April 2022

AbstractThe preparation and thorough characterization of a variety of (arylmethylene)phosphonate ester derivatives (S1–S7) as well as derived geminal bisphosphonate (BP) ester ligands (L1–L7) is presented. Subsequent complexation reactions of CaCl2 with selected BPs (L1–L3) and a known aliphatic tetrakisphosphonate ester (L8) yield the respective Ca(II) coordination compounds [Ca(H2O)2(L1‐‐L3)2]Cl2 (C1‐‐C3) and [Ca(L8)Cl2]n (C4) for potential future application as multi‐delivery systems in osteoporosis treatment. Obtained SCXRD and 1H DOSY‐NMR data provide a detailed insight into their solid‐ as well as solution‐state structures extending the so far scarcely found X‐ray studies on geminal BP‐supported Ca(II) complexes.
Surface‐enhanced Raman Spectroscopy for Versatile in situ Measurements of Local pH near Electrode Surface
Authors: Ide Kohei , Kunimoto Masahiro , Yoshida Satoru , Yanagisawa Masahiro , Homma Takayuki 
Published: April 2022

AbstractWe designed an in situ surface‐enhanced Raman spectroscopy (SERS) system to detect pH change near the electrode surface. An optically transparent substrate covered with Ag nanoparticles (NPs) that induce SERS was positioned vertically to the electrode. A probe molecule that protonates/deprotonates according to the change in pH of surroundings were distributed nearby the NPs, so that the SERS spectrum of the probe indicated the pH changes in the vertical direction to the electrode due to hydrogen consumption. Flexible choices of probe molecules allow the system to be versatile. The system operated effectively in Ni electrodeposition as a case example.
A hybrid attention mechanism for blind automatic modulation classification
Authors: Jia Fan , Yang Yueyi , Zhang Junyi , Yang Yong 
Published: April 2022

AbstractRecently, deep leaning has been making great progress in automatic modulation classification, just like its success in computer vision. However, radio signals with harsh impairments (oscillator drift, clock drift, noise) would significantly degrade the performance of the existing classifiers. To overcome the problem and explore the depth reason, a hybrid attention convolution network is proposed to enhance the capability of feature extraction. First, a spatial transformer network module with long short‐term memory is introduced to synchronize and normalize radio signals. Second, a channel attention module is constructed to weight and assemble feature maps, exploring global feature representations with more context‐relevant information. By combining these two modules, a relatively lightweight classifier with complex convolution layer for final classification is further researched through visualization. Moreover, different structures of attention module are compared and optimized in detail. Experimental result shows that our proposed hybrid model achieves the best performance among all compared models when SNR is upper than 7 dB, and it peaks at 93.448 at 0 dB, 2.7% higher than that of CLDNN and 97.560 at 20 dB, 8.2% higher than that of ResNet. And our model can be more efficient after a trade‐off between accuracy and model size.
Proportional rate constrained resource allocation in multicarrier nonorthogonal multiple access systems
Authors: Ding Hongwen , Li Li 
Published: April 2022

AbstractIn multicarrier nonorthogonal multiple access (MC‐NOMA) systems, resource allocation for user rate fairness is an inherent challenge due to the huge difference in channel conditions among different users. As the general case of proportional fairness, proportional rate constraint is usually adopted in resource allocation optimization problems to ensure that achievable rates of users are distributed proportionally according to a set of arbitrarily predefined portion. In this article, we investigate joint subcarrier and power allocation in MC‐NOMA systems under proportional rate constraints. The formulated resource allocation optimization problem belongs to a mixed integer nonlinear programming (MINLP) problem due to its binary subcarrier allocation variables and nonaffine equality constraints. By introducing an auxiliary variable in proportional rate constraints and substituting power variable with rate variable, we convert this nonconvex problem into a convex optimization problem and solve it by using Karush‐Kuhn‐Tucker (KKT) conditions and the dual decomposition method. Based on the optimal solutions, we divide the resource allocation process into two phases, that is, subcarrier allocation and power allocation, and develop an optimal subcarrier allocation solution based resource allocation algorithm (OSSRA). Furthermore, we also propose a heuristic algorithm, referred to as proportional rate constrained subcarrier allocation algorithm (PCSAA), as a benchmark. Numerical results show that, substantial gains can be achieved by OSSRA over the existing work and the traditional orthogonal multiple access (OMA) schemes in terms of both sum rate and user fairness. Besides, PCSAA has better user fairness performance than OSSRA.
The relationship between dietary acid load and intensity of musculoskeletal pain condition: A population‐based study
Authors: Bahrampour Niki , Clark Cain C. T. 
Published: April 2022

AbstractPain is a globally prevalent problem, and a comprehension of its pathophysiology is important with respect to patient's health. Musculoskeletal pain conditions (MPs) may be associated with physical, lifestyle, and nutrition status, while dietary acid load (DAL) may be inversely associated with musculoskeletal health in adults. This cross‐sectional study consisted of 175 adults experiencing pain. Anthropometric measurements, physical activity (PA), and pain intensity were assessed via specific questionnaires. Dietary data were collected using a 7‐day 24‐h recall. Foods and beverages were analyzed with Nutritionist IV software for extracting the total energy and nutrients. Net endogenous acid production (NEAP) and potential renal acid load (PRAL) were evaluated for assessing the DAL. Linear regression and Spearman correlation were used to investigate the association of exposure and input variables. Linear regression showed a positive relationship between PRAL and NEAP and pain intensity in the crude model. This significant positive relationship remained after adjusting for all confounders. A lower consumption of potassium, magnesium, vitamin B9 and C, and fiber was seen in the following quartiles of PRAL and NEAP. In addition, MPs intensity and PRAL and NEAP had a weak, positive correlation. This study suggests that a higher DAL may be associated with MPs. However, further research is needed.
Content of industrially produced trans fatty acids in breast milk: An observational study
Authors: Bousset‐Alféres Christian Mayela , Chávez‐Servín Jorge Luis , Vázquez‐Landaverde Pedro Alberto , Betancourt‐López Claudia Azucena , Caamaño María del Carmen , Ferriz‐Martínez Roberto Augusto , Chávez‐Alabat Elsa Fernanda , Lovatón‐Cabrera Ma Guadalupe , de la Torre‐Carbot Karina 
Published: April 2022

AbstractBreast milk may contain industrially produced trans fatty acids (TFAs), which can affect the content of essential fatty acids (EFAs). This could have significant implications for the child's development. The fatty acids present in breast milk can be modified by adjusting the mother's diet. The objective of this study was to determine the content of industrially produced TFAs present in colostrum, transitional milk, and mature milk produced by mothers between 18 and 45 years of age in the state of Querétaro, Mexico, based on a longitudinal observational study. The TFA content in the breast milk of 33 lactating women was analyzed using gas chromatography. The mothers’ consumption of TFAs was also estimated by analyzing a log prepared through 24‐hr dietary recall (24HR) obtained in each period. The TFA content in the mothers’ diet was similar across the colostrum, transitional milk, and mature milk phases: 1.64 ± 1.25 g, 1.39 ± 1.01, and 1.66 ± 1.13 g, respectively. The total TFA content was 1.529% ± 1.648% for colostrum; 0.748% ± 1.033% for transitional milk and 0.945% ± 1.368% for mature milk. Elaidic acid was the TFA in the highest concentration in all three types of milk. No correlation was found between the content of industrially produced TFAs in breast milk and the anthropometric measurements of the mother or between the estimated consumption of TFAs and the content of TFAs in breast milk. Elaidic acid and total content of TFAs were negatively correlated (p < .05) with the content of docosahexaenoic acid (DHA) (0.394 ± 0.247) (R = −0.382) in colostrum. The concentration of TFAs was found to correlate with the composition of EFAs in milk.
Effects of alfalfa meal on quality and function of pork meatballs
Authors: Xu Zhifeng , Du Yushuang , Li Na , Geng Hongmin , Ali Qasim , Li Xinbo , Gao Yajun , Wang Yan , Xing Ronghui , Wu Jie , Cui Fangjie , Wang Chengzhang , Zhu Xiaoyan , Cui Yalei , Li Defeng , Shi Yinghua 
Published: April 2022

AbstractAlfalfa (Medicago sativa L.) is abundant in dietary fiber, alfalfa saponins, and other active ingredients. However, the application of alfalfa is scarce in food. Meatball is one of the most popular meat products in daily life, but eating too many meatballs could result in obesity, hyperlipidemia, and other diseases. With increasing attention to healthy diet, how to keep the original color, aroma, taste, and shape of food with low fat and nutrition has become an urgent problem to be solved. In this study, different amounts of alfalfa meal or extruded alfalfa meal were added to pork meatballs to explore the optimal adding ratio of two kinds of alfalfa meal in pork meatballs. Further animal experiments were conducted for two weeks to prove the efficacy of two kinds of alfalfa balls in lowering blood lipid and body weight. The results showed that 0.5% alfalfa meal and 1% extruded alfalfa meal could improve the quality of prepared pork meatballs. Animal experiments demonstrated that two kinds of alfalfa meal pork meatballs had a good effect of reducing blood lipid, and the alfalfa meal pork meatballs had a better effect on reducing serum cholesterol and average daily weight gain of mice. This study provided a theoretical basis for making healthy and nutritious pork meatballs, which could provide more delicious food for people, especially people who are obese and the elderly.
Does offshore NDF market influence onshore forex market? Evidence from India
Authors: Behera Harendra , Ranjan Rajiv , Chinoy Sajjid 
Published: April 2022

AbstractThe paper uses a vector error correction model–multivariate generalized autoregressive conditional heteroskedasticity approach to examine the interrelationship between onshore and offshore nondeliverable forward (NDF) markets for the Indian Rupee. The empirical results suggest a stable and bidirectional long‐run relationship between onshore and offshore markets. The subperiod analysis implies that there are unidirectional mean spillovers from NDF markets to onshore spot, forward, and futures markets during the post‐taper tantrum period. Regarding “volatility spillover,” the analysis indicates a unidirectional volatility spillover from spot and forward segments to NDF market in normal circumstances, which turns bidirectional during times of depreciation pressure on the rupee.