bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically‐based pharmacokinetic modeling to predict CYP3A4‐mediated drug‐drug interactions of finerenone
Authors: Wendl Thomas , Frechen Sebastian , Gerisch Michael , Heinig Roland , Eissing Thomas 
Published: November 2021

AbstractFinerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist that recently demonstrated its efficacy to delay chronic kidney disease (CKD) progression and reduce cardiovascular events in patients with CKD and type 2 diabetes. Here, we report the development of a physiologically‐based pharmacokinetic (PBPK) model for finerenone and its application as a victim drug of cytochrome P450 3A4 (CYP3A4)‐mediated drug‐drug interactions (DDIs) using the open‐source PBPK platform PK‐Sim, which has recently been qualified for this application purpose. First, the PBPK model for finerenone was developed using physicochemical, in vitro, and clinical (including mass balance) data. Subsequently, the finerenone model was validated regarding the contribution of CYP3A4 metabolism to total clearance by comparing to observed data from dedicated clinical interaction studies with erythromycin (simulated geometric mean ratios of the area under the plasma concentration‐time curve [AUCR] of 3.46 and geometric mean peak plasma concentration ratios [CmaxRs] of 2.00 vs. observed of 3.48 and 1.88, respectively) and verapamil (simulated AUCR of 2.91 and CmaxR of 1.86 vs. observed of 2.70 and 2.22, respectively). Finally, the finerenone model was applied to predict clinically untested DDI studies with various CYP3A4 modulators. An AUCR of 6.31 and a CmaxR of 2.37 was predicted with itraconazole, of 5.28 and 2.25 with clarithromycin, 1.59 and 1.40 with cimetidine, 1.57 and 1.38 with fluvoxamine, 0.19 and 0.32 with efavirenz, and 0.07 and 0.14 with rifampicin. This PBPK analysis provides a quantitative basis to guide the label and clinical use of finerenone with concomitant CYP3A4 modulators.
CD8αα+T Cells Exert a Pro-Inflammatory Role in Patients with Psoriasis
Authors: Zhang Y. Y. , Lin Y. T. , Wang L. , Sun X. W. , Dang E. L. , Xue K. , Zhang W. G. , Zhang K. M. , Wang G. , Li B. 
Published: November 2021

Abstract

Background
Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4+T cells, including Th17, Th1 and Th22. The role of CD8+T cells in psoriasis pathogenesis remains poorly understood.

Aim
To identify the phenotype of CD8+T cells in patients with psoriasis and to investigate its role in the formation of lesions.

Methods
The phenotype of CD8+T cells in psoriatic lesions was detected by immunofluorescence staining. Flow cytometry was performed to detect their phenotype in peripheral blood. Thereafter, coculture of CD8αα+T cells with autogenous CD4+T cells was performed to investigate the function of CD8αα+T cells in patients with psoriasis. Finally, pro-inflammatory factors produced by CD8αα+T cells were examined by immunofluorescence staining and flow cytometry.

Results
Compared to the CD8αβ+T cells, CD8αα+T cell infiltration in psoriatic lesions markedly increased. Moreover, epidermal CD8αα+T cells exhibited tissue-resident memory T cells (TRM) phenotypes and dermal CD8αα+T cells exhibited effector memory (TEM) phenotypes in psoriatic lesions. Additionally, we found that CD8αα+T cells from patients with psoriasis did not express the markers of regulatory T cells and could promote the proliferation of CD4+T effector cells and produce interleukin-17 and interferon-γ.

Conclusions
Our findings demonstrate that CD8αα+T cells contribute to the pathogenesis of psoriasis by producing pro-inflammatory factors.
Clinical Characteristics and Management of Acute Generalized Exanthematous Pustulosis with Haemodynamic Instability
Authors: O’Brian M. , Carr C. L. , Thomas C. , Dominguez A. R. , Mauskar M. 
Published: November 2021

Abstract

Background
Acute generalized exanthematous pustulosis (AGEP) is a severe pustular drug eruption with rare reports of haemodynamic instability.

Objective
To describe the clinical characteristics, management, and outcomes of patients with AGEP-associated haemodynamic instability.

Methods
This retrospective case series identified adult patients diagnosed with AGEP who had haemodynamic instability from November 2012 to February 2020 that were seen at two academic teaching hospitals with roles as a burn centre and tertiary referral centre at the University of Texas Southwestern Medical Center in Dallas, TX USA. Patients with a discharge diagnosis of AGEP that had haemodynamic instability during their eruption were included. Patients with a history of psoriasis, presentations thought to be a flare of generalized pustular psoriasis, or concurrent infection during eruption were excluded. AGEP with haemodynamic instability was characterized by degree of hypotension, dermatologic phenotype at time of dermatologic consultation, and management approach.

Results
This study included 19 patients with AGEP-associated haemodynamic instability (mean age, 52 years; age range, 29–76 years; 11 (58%) female). Patients were classified on a spectrum of haemodynamic instability; three had sustained hypotension, 10 had hypotension with organ dysfunction, and six had shock. Patients with AGEP-associated haemodynamic instability had a range of dermatologic phenotypes at initial consultation: subtle exanthematous eruption with minimal pustules, typical eruption with pustules and flexural predominance, and severe eruption with features of Stevens–Johnson syndrome. Both topical and systemic corticosteroids were used for treatment of several patients. Of the patients that required vasopressors and received systemic steroids, the majority were off vasopressors within 24 h of steroid initiation.

Conclusion
Approximately 22% of patients presenting with AGEP to a tertiary referral center had haemodynamic instability. Clinicians should be aware that dermatologic phenotype of AGEP at presentation does not correlate with development of haemodynamic instability.
Microdermabrasion Facilitates Direct Current Stimulation by Lowering Skin Resistance
Authors: Chhatbar P. Y. , Liu S. , Ramakrishnan V. , George M. S. , Kautz S. A. , Feng W. 
Published: November 2021

Abstract

Background
Transcranial direct current stimulation (tDCS) is reported to induce irritating skin sensations and occasional skin injuries, which limits the applied tDCS dose. Additionally, tDCS hardware safety profile prevents high current delivery when skin resistance is high.

Objective
To test if decreasing skin resistance can enable high-dose tDCS delivery without increasing tDCS-related skin sensations or device hardware limits.

Methods
We compared the effect of microdermabrasion and sonication on 2 mA direct current stimulation (DCS) through forearm skin for 2–3 min on 20 subjects. We also surveyed the subjects using a questionnaire throughout the procedure. We used a linear mixed-effects model for repeated-measures and multiple logistic regression, with adjustments for age, race, gender and visit.

Results
Microdermabrasion, with/out sonication, led to significant decrease in skin resistance (1.6 ± 0.1 kΩ or ~32% decrease, p &lt; 0.0001). The decrease with sonication alone (0.4 ± 0.1 kΩ or ~7% decrease, p = 0.0016) was comparable to that of sham (0.3 ± 0.1 kΩ or ~5% decrease, p = 0.0414). There was no increase in the skin–electrode interface temperature. The perceived DCS-related sensations did not differ across skin preparation procedures (p &gt; 0.16), but microdermabrasion (when not combined with sonication) led to increased perceived sensation (p &lt; 0.01).

Conclusions
Microdermabrasion (with/out sonication) resulted in reduced skin resistance without increase in perceived skin sensations with DCS. Higher current can be delivered with microdermabrasion-pre-treated skin without changing the device hardware while reducing, otherwise higher voltage required to deliver the same amount of current.
Impact of Coordination Modes of N‐Donor Ligands on Am(III)/Eu(III) Separation in Nuclear Waste Water Treatment – A DFT Study
Authors: Ebenezer Cheriyan , Solomon Rajadurai Vijay 
Published: November 2021

AbstractDetection and degradation of environmental pollutants is always a challenging task, especially in nuclear waste management. The presence of radioactive minor actinides in the spent nuclear fuel from nuclear reactors leads to adverse effects on both humans and the environment. In this context, designing ligands plays a pivotal role in the partitioning process of actinides from lanthanides. Though we have many ligands with varying coordination modes reported, one needs to look deeper into the role and number of coordinating atoms of a ligand to gain a basic understanding of the extraction process. Hence, N‐donor ligands (Pypz, BTP, BTPhen and TPDCA) with a different number of coordinating atoms (two, three, four and five) and their Am/Eu complexes have been considered for this study. Exhaustive density functional theory calculations have been carried out to get an essence of the coordination chemistry of ML(NO3)3 complexes and how the number of coordinating atoms impacts the selectivity towards Am3+ over Eu3+ ions. The calculated thermodynamic parameters shed light on the selectivity of these ligands towards Am(III) over Eu(III). Results reveal that the BTP ligand shows the best selectivity out of all the ligands. We found that the higher the number of coordination modes higher will be the binding energy. However, the selectivity depends on the strength and nature of M−L bonds. In brief, this study offers us insights into the tailoring of ligands with an optimum number of coordinating atoms for Am(III)/Eu(III) stripping in the spent nuclear waste processing.
Preparation of Polyvinyl alcohol Hydrogel Braided Wire Reinforced by Soluble starch Granules Based on Magnetoionic induction and Piezoelectric sensing
Authors: Liu Zhiqiang , Fan Jinqiang , Zou Minggui , Ma Xu , Niu Yan , Gong Guifen 
Published: November 2021

AbstractIntegrating textiles with a signal collector may provide sustainable solutions for wearable electronic devices in the Internet of Things era owing to the soaring development of chemistry and materials. This study adopted soluble starch(S) granules for advancing the resistance and formability of polyvinylalcohol (PVA) hydrogel in the structural deformation stage, thus preparing a PVA based composite hydrogel wire that may be produced continuously. In the whole process, the mechanical performance, strain resistance and sensing property of the hydrogel wire were studied. The results showed that when PVA : S=7 : 3, the hydrogel wire had the best formability and mechanical performance, and the stress and strain were 2.3 MPa and 255 % respectively. When starch granules were added in the hydrogel wire, the coincidence degree between starting stress and cyclic stress was increased after the wire was stretched by 17.5 %, and thus, the stability of the hydrogel wire was improved. In addition, the electronic skin strain sensors assembled with hydrogel wires can detect the movement of different parts of the body effectively. In particular, a piezoelectric sensor braided with polyurethane‐encapsulated hydrogel wire may not only generate a voltage about 0.4 mV at a slight touch, but also locate the stress point. When an induction coil is prepared with the hydrogel wire, the magnetoionic induction of a single coil can produce a significant induced voltage, which is conductive to the wireless signal transmission of hydrogel. As a conductor, the hydrogel wire also had a current reaction in phase to AC voltage. And according to the experiment, it is speculated that as braided and electronically integrated, the hydrogel wire can be used in smart fabrics for strain sensing, wireless signal transmission, and force location.
Infection Medications: Assessment In‐Vitro Glutathione S‐Transferase Inhibition and Molecular Docking Study
Authors: Türkeş Cüneyt , Demir Yeliz , Beydemir Şükrü 
Published: November 2021

AbstractGlutathione S‐transferases (EC 2.5.1.18, GSTs), consisting of at least seven subfamilies, such as alpha, kappa, mu, pi, theta, zeta, and omega, are the family of cytosolic proteins with many known functions and also are abundant in cells. Moreover, they play significant roles in influencing the efficacy and bioavailability of pharmaceutical agents in humans. It is also known that multiple types of cancer tissue frequently have high levels of GSTs compared to the corresponding healthy tissue. Herein, firstly, the GST was purified from human erythrocytes by rapid and straightforward chromatographic techniques. Subsequently, the active infection medications, the antimycotics (amphotericin B, anidulafungin, and caspofungin), antibacterials (daptomycin, ertapenem, and tigecycline), and antiviral (ganciclovir) were assessed for their inhibitory actions versus GST. All drugs demonstrated micromolar levels of potent inhibitory activity towards GST. Antifungal drugs had KI constants ranging between 20.60±0.05 μM and 50.43±0.12 μM, whilst antibacterial drugs exhibited KIs in the range of 20.92±0.09–114.80±0.41 μM. Daptomycin and ertapenem exhibited competitive inhibition, while other drugs in noncompetitive inhibition. Moreover, amphotericin B exhibited the most potent inhibitory activity (KI=20.60±0.05 μM), and in contrast, antiviral drug ganciclovir had the highest inhibition constant (KI=463.10±1.28 μM). Studying both in‐vitro inhibitory activity and molecular docking interactions in silico activities of these infection medications in complex with the GST, an enzyme biologically important, demonstrates was caused significant associations between these drugs and GST were detected. The results here might provide structural guidance to design more potent GST inhibitors.
Synthesis of β‐Chloro‐α‐hydroxyphosphonates through Triethylamine‐Catalyzed Pudovik Reaction
Authors: Guo Huichuang , Cao Yuepeng , Zhang Yulong , Wu Qian , Liu Haibo , Yuan Ling , Liu Changcai , Guo Yongbiao , Shi Enxue 
Published: November 2021

AbstractVersatile β‐chloro‐α‐hydroxyphosphonates were synthesized in high yields from α‐chloroketones and phosphites based on the efficient control of competitive Pudovik/Arbuzov/Perkow reactions. Triethylamine was found most efficient to catalyze the Pudovik reaction regioselectively under mild solvent‐free conditions. Aliphatic, aromatic, cyclic α‐chloroketones and phosphonites/phosphinites were also applicable to this practical column‐free procedure.
Acquired employees versus hired employees: Retained or turned over?
Authors: Ng Weiyi , Stuart Toby E. 
Published: November 2021

AbstractResearch SummaryThousands of acquisitions of technology companies result in the de facto hiring of myriad individuals into new employers every year. We analyze the effects of such deals on acquired employee (AE) retention relative to a matched sample of directly hired employees (HEs) joining the same acquirers in the same year. In a dataset with all acquisitions of VC‐backed companies in the previous two decades paired to over 30 million resumes, we find that acquired employees (AEs) turnover at a much higher rate than matched, HEs. Importantly, this difference in turnover rates is larger for AEs in higher job ranks and with advanced degrees. Likewise, we show that the postacquisition departure rate is highest for AEs in critical executive, technical, business development, and sales roles.Managerial SummaryAcquisitions of venture‐backed tech‐companies occur for many strategic reasons, including the acquisition of key managerial and technical human talent. The retention of acquired talent is thus an important consideration for the value of the acquisition. Through a dataset of over 30 million resumes, we examine the turnover rates of employees acquired through technology acquisitions in the previous two decades, comparing these AEs to their similar, organically hired counterparts. In this comparison, we find that AEs are more likely to turnover in general. Importantly, the higher turnover rate of AEs increases with seniority and education attainment and is the highest in critical executive, technical, business development, and sales roles.
Catch and Release Chemotaxis
Authors: Yasugahira Yusuke , Tatsumi Yuki , Yamanaka Osamu , Nishimori Hiraku , Nagayama Masaharu , Nakata Satoshi 
Published: November 2021

AbstractCatch and release chemotaxis was studied by using a self‐propelled 6‐methylcoumarin (6‐MC) disk floating on water. A tablet of Na3PO4 placed at the bottom of the water phase acted as a chemical stimulus. The repetition of catch and release chemotaxis, that is, the alternating inversion of the spatial gradient of surface tension, was realized using one 6‐MC disk and one Na3PO4 tablet. Alternating catch and release chemotaxis was observed using two 6‐MC disks and one Na3PO4 tablet. The mechanism of catch and release chemotaxis is discussed in relation to the change in the surface tension of the 6‐MC aqueous phase following the addition of Na3PO4 as the driving force, the spatial concentration gradient of the base dissolved from the tablet in the water phase, and the chemical reaction between 6‐MC and OH−. Understanding this type of chemotaxis system can elucidate the chemotaxis behaviors of living organisms.
Cognitive and metacognitive, motivational, and resource considerations for learning new skills across the lifespan
Authors: Sheffler Pamela , Rodriguez Tania M. , Cheung Cecilia S. , Wu Rachel 
Published: November 2021

AbstractAcross the lifespan, learners have to tackle the challenges of learning new skills. These skills can range from abilities needed for survival, such as learning languages, learning to walk during infancy, and learning new software for a job in adulthood, to abilities related to leisure and hobbies. As the learner progresses through novice to expert stages, there are cognitive and metacognitive, motivational, and resource considerations for learning new skills. In terms of cognitive considerations, fluid and crystallized abilities as well as executive functions interact to help the learner process and retain information related to the skills. In terms of metacognitive considerations, knowing what to learn and how to learn are important for novel skill learning. In terms of motivational considerations, changes in individuals' intrinsic and extrinsic motivation throughout the lifespan impact their pursuit of novel skill learning, and declines in motivation can be buffered through the cultivation of grit, growth mindset, self‐efficacy, and other personal factors. In terms of resource considerations, there are many tools that learners can use to acquire new skills, but allocation and availability of these resources differ based on life stage and socioeconomic status. Taken together, these considerations may provide learners with the best chance at acquiring new skills across the lifespan. Further research investigating these three factors, particularly among older adult learners, and their interactive effects could help increase our understanding of their impacts on skill learning and inform future cognitive interventions that can be tailored to learners' unique needs.This article is categorized under:Cognitive Biology > Cognitive DevelopmentPsychology > Development and AgingPsychology > Learning
The Bur1 cyclin‐dependent kinase regulates telomere length in Saccharomyces cerevisiae
Authors: Connelly Carla J. , Vidal‐Cardenas Sofia , Goldsmith Stephanie , Greider Carol W. 
Published: November 2021

AbstractTelomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin‐dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin‐dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1∆ and bur2∆ set2∆ were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin‐dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2∆ set2∆ mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation.
Re-Theorising Spatial Segregation: A European Perspective
Authors: Piekut Aneta 
Published: November 2021

AbstractResearch on segregation is traditionally associated with studies on residential segregation and the patterns of spatial clustering of minority ethnic groups or residents with immigrant backgrounds. This chapter examines European research on spatial segregation through various social science disciplines, including urban studies, sociology, psychology, spatial and human geography. It presents the range of theoretical approaches employed to explain why people who belong, or are perceived to belong, to dissimilar social categories or to hold different identities become spatially separated from each other, and ways in which this may change. Factors that influence segregation are interrelated. A holistic, interdisciplinary approach to spatial segregation is, therefore, essential to understand such mechanisms and then design policies to counter any negative impacts of segregation. Individual and group experiences are shaped by varied contexts, whether residential, work, leisure, transport and daily encounters. This chapter examines approaches to spatial segregation from a variety of disciplinary perspectives and indicates possible directions for future research.
Income Inequality and Residential Segregation in European Cities
Authors: Tammaru Tiit , Sinitsyna Anastasia , Akhavizadegan Alireza , van Ham Maarten , Marcińczak Szymon , Musterd Sako 
Published: November 2021

AbstractBasedonextensiveresearchwithdistinguished scholars within the book project ‘Socioeconomic Segregation in European Capital Cities’, this chapter summarizes the key trends in income inequalityand socioeconomic segregationin Europe. We draw our data from the two last census rounds, and we focus on the most common indicators of incomeinequality(Gini Index) and residential segregation(DissimilarityIndex). We find that levels of residential segregation grew between the two last censuses in most of the cities included in our study. Changes in residential segregation follow changes in income inequality with a time lag, and it tends to happen in both directions. Low levels of income inequality relate to low levels of segregation after 10 years, and high levels of inequality relate to high levels of segregation after 10 years.