bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of primary cilia‐positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation
Authors: Shinmura Kazuya , Kusafuka Kimihide , Kawasaki Hideya , Kato Hisami , Hariyama Takahiko , Tsuchiya Kazuo , Kawanishi Yuichi , Funai Kazuhito , Misawa Kiyoshi , Mineta Hiroyuki , Sugimura Haruhiko 
Published: May 2021

AbstractPrimary cilia (PC) are non‐motile, antenna‐like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron‐microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC‐positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC‐positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC‐positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour‐specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Optimized selection of nanohydroxyapatite‐filled dental restorative composites formulation for best physico‐mechanical, chemical, and thermal properties using hybrid analytical hierarchy process‐multi‐objective optimization on the basis of ratio analysis approach
Authors: Gangwar Swati , Yadav Sukriti , Pathak Vimal Kumar 
Published: May 2021

AbstractThe present research explored and optimized dental restorative composite (DRC) materials filled with nanohydroxyapatite (n‐HAP) based on their physico‐mechanical, chemical, and thermal properties. In the same context, hybrid analytical hierarchy process (AHP) and multi‐objective optimization on the basis of ratio analysis (MOORA) approach was proposed to select the best DRC with optimal combination of physico‐mechanical, chemical, and thermal properties. Seven formulations based on Bis‐GMA as a base monomer with APTES ((3‐aminopropyl) triethoxysilane) and MPTS ((3‐methacryloxypropyl) trimethoxy silane) silane‐treated n‐HAP as a filler were developed and examined for different characteristics. The experiments performed for evaluating various properties of fabricated DRCs formulations are as per the ASTM and ISO 4049 standards. The experimental results proved that APTES‐ and MPTS‐treated n‐HAP enhances the physico‐mechanical as well as chemical and thermal performance significantly. The DRCs show better sorption and solubility behavior when silane‐treated n‐HAP filler increases and remains in the acceptable range. The optimization of prepared samples was carried out in two phases: (a) finding weight of each attributes using AHP approach and (b) ranking the samples with MOORA approach. The hybrid AHP‐MOORA results depict that optimal combination of physical, mechanical, chemical, and thermal characteristics was exhibited by the DRC sample with 8 wt% MPTS‐treated n‐HAP filler.
Drug product dispensing and estimates of use in a general population survey as a signal detection problem
Authors: Black Joshua C. , Forber Alyssa , Severtson S. Geoff , Rockhill Karilynn , May K. Patrick , Amioka Elise , Schwarz John , Iwanicki Janetta , Dart Richard C. 
Published: May 2021

AbstractPurposeUnderstanding potential bias due to rarity of the outcome is important when monitoring newly approved drugs and drugs with low availability to the general public. Although there is an increasing use of online surveys to investigate health outcomes, the limits of inference due to drug availability have not been studied. The goal of this study was to quantify the relationship between dispensing of prescription drugs and estimates of use in an online general population survey.MethodsAn online repeated, cross‐sectional survey from 2018 to 2020 was used to estimate the number of adults in the United States who used prescription drugs in the general population and compared to estimated number of prescriptions dispensed over an equivalent time period. Joinpoint regression was used to quantify thresholds. A sample of respondents was retested to estimate reliability statistics.ResultsA model with a single threshold was the best fit, with the estimated threshold of 565 000 (95% CI: 9500‐11 600 000) prescriptions dispensed per year. Above the threshold, there was a significant association between dispensing and estimates (p < 0.001); below the threshold, the relationship was not significant (p = 0.912). Above the threshold, responses were more reliable than random chance, and reliability steadily increased with increased dispensing.ConclusionsThese results suggest the threshold demarcates two distinct pharmacoepidemiological paradigms when investigating drug use in general population surveys. Dispensing can be used as a guide to determine the epidemiological paradigm that is best suited.
Epitope mapping of novel monoclonal antibodies to human angiotensin I‐converting enzyme
Authors: Popova Isolda A. , Lubbe Lizelle , Petukhov Pavel A. , Kalantarov Gavriil F. , Trakht Ilya N. , Chernykh Elena R. , Leplina Olga Y. , Lyubimov Alex V. , Garcia Joe G.N. , Dudek Steven M. , Sturrock Edward D. , Danilov Sergei M. 
Published: May 2021

AbstractAngiotensin I‐converting enzyme (ACE, CD143) plays a crucial role in blood pressure regulation, vascular remodeling, and immunity. A wide spectrum of mAbs to different epitopes on the N and C domains of human ACE have been generated and used to study different aspects of ACE biology, including establishing a novel approach–conformational fingerprinting. Here we characterized a novel set of 14 mAbs, developed against human seminal fluid ACE. The epitopes for these novel mAbs were defined using recombinant ACE constructs with truncated N and C domains, species cross‐reactivity, ACE mutagenesis, and competition with the previously mapped anti‐ACE mAbs. Nine mAbs recognized regions on the N domain, and 5 mAbs–on the C domain of ACE. The epitopes for most of these novel mAbs partially overlap with epitopes mapped onto ACE by the previously generated mAbs, whereas mAb 8H1 recognized yet unmapped region on the C domain where three ACE mutations associated with Alzheimer's disease are localized and is a marker for ACE mutation T877M. mAb 2H4 could be considered as a specific marker for ACE in dendritic cells. This novel set of mAbs can identify even subtle changes in human ACE conformation caused by tissue‐specific glycosylation of ACE or mutations, and can detect human somatic and testicular ACE in biological fluids and tissues. Furthermore, the high reactivity of these novel mAbs provides an opportunity to study changes in the pattern of ACE expression or glycosylation in different tissues, cells, and diseases, such as sarcoidosis and Alzheimer's disease.
Can new herbicide discovery allow weed management to outpace resistance evolution?
Authors: Gaines Todd A , Busi Roberto , Küpper Anita 
Published: May 2021

AbstractWhile herbicides are the most effective and widely adopted weed management approach, the evolution of multiple herbicide resistance in damaging weed species threatens the yield and profitability of many crops. Weeds accumulate multiple resistance mechanisms through sequential selection and/or gene flow, with long‐range and international transport of herbicide‐resistant weeds proving to be a serious issue. Metabolic resistance mechanisms can confer resistance across multiple sites of action and even to herbicides not yet discovered. When a new site of action herbicide is introduced to control a key driver weed, it likely will be one of very few effective available herbicide options for that weed in a specific crop due to the continuous use of herbicides over the years and the resulting accumulation of resistance mechanisms, placing it at even higher risk to be rapidly lost to resistance due to the high selection pressure it will experience. The number of available, effective herbicides for certain driver weeds is decreasing over time because the rate of resistance evolution is faster than the rate of new herbicide discovery. Effective monitoring for species movement and diagnostics for resistance should be deployed to rapidly identify emerging resistance to any new site of action. While innovation in herbicide discovery is urgently needed to combat the pressing issue of resistance in weeds, the rate of selection for herbicide resistance in weeds must be slowed through changes in the patterns of how herbicides are used. © 2021 Society of Chemical Industry. © 2021 Society of Chemical Industry.
Welfare and social protection: What is the link with secondary migration? Evidence from the 2014‐crisis hit Italian region of Lombardy
Authors: Ortensi Livia Elisa , Barbiano di Belgiojoso Elisa 
Published: May 2021

AbstractEvidence on the relationship between secondary international migration and welfare state (or formal protection) support is currently limited. Also, the experience of financial support from semiformal and informal social protection networks has seen limited inclusion in current reflections on secondary mobility patterns such as onward and return migration. Our study analyses the relationship between support from formal, informal and semiformal social protection and short‐term secondary migration intentions. The study uses open‐access data from the Regional Observatory for Integration and Multiethnicity of Lombardy (Italy) and adopts a competing‐risk framework through multinomial logistic regression. Our data do not support the hypothesis of an ex‐post “magnetic effect” of the Italian formal social protection on its beneficiaries: individuals on formal welfare are more prone to onward and return migration. However, the positive relationship observed between welfare entitlements and onward migration intentions cannot rule out any effect of welfare magnetism from more generous welfare systems. Monetary aid received from Italian friends is negatively related to return intention. At the same time, economic support from foreign‐born friends is correlated to return migration. We interpret results according to social network theory. Economic support and social capital from bridging networks can act as an ex‐post integration‐driven magnet. Bonding social capital from ties with migrants in Italy cannot secure the migrants' stay in Italy. However, it can support return migration. Networks providing bonding transnational social capital, and expressed in the form of financial support from relatives living abroad, are instead positively correlated to both forms of secondary migration.
End‐to‐end application of model‐informed drug development for ertugliflozin, a novel sodium‐glucose cotransporter 2 inhibitor
Authors: Fediuk Daryl J. , Nucci Gianluca , Dawra Vikas K. , Callegari Ernesto , Zhou Susan , Musante Cynthia J. , Liang Yali , Sweeney Kevin , Sahasrabudhe Vaishali 
Published: May 2021

AbstractModel‐informed drug development (MIDD) is critical in all stages of the drug‐development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end‐to‐end development of ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose–response relationships, (2) dose–response modeling and model‐based meta‐analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose‐proportionality and the impact of uridine 5'‐diphospho‐glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically‐based PK modeling to assess the risk of UGT‐mediated drug–drug interactions. These end‐to‐end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling.
A generic framework for the physiologically‐based pharmacokinetic platform qualification of PK‐Sim and its application to predicting cytochrome P450 3A4–mediated drug–drug interactions
Authors: Frechen Sebastian , Solodenko Juri , Wendl Thomas , Dallmann André , Ince Ibrahim , Lehr Thorsten , Lippert Jörg , Burghaus Rolf 
Published: May 2021

AbstractThe success of applications of physiologically‐based pharmacokinetic (PBPK) modeling in drug development and drug labeling has triggered regulatory agencies to demand rigorous demonstration of the predictive capability of the specific PBPK platform for a particular intended application purpose. The effort needed to comply with such qualification requirements exceeds the costs for any individual PBPK application. Because changes or updates of a PBPK platform would require (re‐)qualification, a reliable and efficient generic qualification framework is needed. We describe the development and implementation of an agile and sustainable technical framework for automatic PBPK platform (re‐)qualification of PK‐Sim® embedded in the open source and open science GitHub landscape of Open Systems Pharmacology. The qualification approach enables the efficient assessment of all aspects relevant to the qualification of a particular purpose and provides transparency and traceability for all stakeholders. As a showcase example for the power and versatility of the qualification framework, we present the qualification of PK‐Sim® for the intended purpose of predicting cytochrome P450 3A4 (CYP3A4)–mediated drug–drug interactions (DDIs). Several perpetrator PBPK models featuring various degrees of CYP3A4 modulation and different types of mechanisms (competitive inhibition, mechanism‐based inactivation, and induction) were coupled with a set of PBPK models of sensitive CYP3A4 victim drugs. Simulations were compared to a comprehensive data set of 135 observations from published clinical DDI studies. The platform's overall predictive performance showed reasonable accuracy and precision (geometric mean fold error of 1.4 for both area under the plasma concentration‐time curve ratios and peak plasma concentration ratios with/without perpetrator) and suggests that PK‐Sim® can be applied to quantitatively assess CYP3A4‐mediated DDI in clinically untested scenarios.
Acoustic radiation force impulse elastography: a tool for muscle aging assessment: a pilot study
Authors: Regueme Sophie C. , Frulio Nora , Trillaud Hervé , Laurent Christophe , Rullier Eric , Dallaudière Benjamin , Bourdel‐Marchasson Isabelle 
Published: May 2021

AbstractBackgroundCAPARFI study explored whether sonoelastographic data collected using the acoustic radiation force impulse (ARFI) system are reliable when evaluating skeletal muscles and whether the technique can detect muscle changes with aging.MethodsTwenty young (YH; 18–30 years) and 30 old (OH; ≥70 years) healthy volunteers and 15 old patients with cancer (OP; ≥70 years) were assessed through quantitative ARFI measurements (m s−1) of the relaxed rectus femoris, tibialis anterior, and soleus muscles, and Short Physical Performance Battery (SPPB) test. The reliability in ARFI measurements was evaluated by intra‐class correlation coefficient. Among‐group differences in ARFI measurements and SPPB were evaluated using a global linear model.ResultsAcoustic radiation force impulse measurements demonstrated high reliability in all groups (intra‐class correlation coefficient > 0.82). ARFI measurements of the rectus femoris muscle were significantly lower in both the OH and OP groups than in the YH group (1.46 ± 0.12 and 1.50 ± 0.32 vs. 1.80 ± 0.35 m s−1). The ARFI measurements of the soleus muscle were significantly lower in the OP group than in the YH group (1.37 ± 0.37 vs. 1.70 ± 0.53 m s−1). No significant difference was observed for tibialis anterior muscle. Significantly lower SPPB scores were observed in the OP group (10.3 ± 1.4 out of 12) than in the YH (12.0 ± 0.0) and OH groups (11.5 ± 1.0).ConclusionsThis study demonstrated that ARFI quantitative measurements are reliable in relaxed skeletal muscle and may be reliably used to explore muscle changes with aging and/or neoplasia in clinical practice.
Long‐term response to osimertinib in elderly patients with lung adenocarcinoma harbouring de novo EGFR T790M: a case report and literature review
Authors: Sumi Toshiyuki , Kamada Koki , Shijubou Naoki , Yamada Yuichi , Nakata Hisashi , Mori Yuji , Chiba Hirofumi 
Published: May 2021

AbstractOsimertinib is a potent and irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively acts on both EGFR‐sensitive and EGFR T790M‐resistant mutations. Patients with pre‐treatment EGFR T790M mutations (de novo EGFR T790M) respond poorly to existing EGFR‐TKIs, whereas osimertinib has positive effects. However, the safety data for first‐line osimertinib treatment in patients aged >75 years are insufficient. We treated two elderly patients with de novo EGFR T790M mutations with osimertinib as the first‐line therapy. We found that the first‐line treatment with osimertinib was safe and resulted in a long‐term response in elderly patients with de novo EGFR T790M‐mutated lung adenocarcinoma.
Donor-Defined Mesenchymal Stem Cell Antimicrobial Potency Against Nontuberculous Mycobacterium
Authors: Bonfield Tracey L. , Sutton Morgan T. , Fletcher David R. , Folz Michael A. , Ragavapuram Vaishnavi , Somoza Rodrigo A. , Caplan Arnold I. 
Published: May 2021

Abstract
Chronic nontuberculous mycobacterial infections with Mycobacterium avium and Mycobacterium intracellulare complicate bronchiectasis, chronic obstructive airway disease, and the health of aging individuals. These insidious intracellular pathogens cause considerable morbidity and eventual mortality in individuals colonized with these bacteria. Current treatment regimens with antibiotic macrolides are both toxic and often inefficient at providing infection resolution. In this article, we demonstrate that human marrow-derived mesenchymal stem cells are antimicrobial and anti-inflammatory in vitro and in the context of an in vivo sustained infection of either M. avium and/or M. intracellulare.
Six‐Degree‐of‐Freedom Steerable Visible‐Light‐Driven Microsubmarines Using Water as a Fuel: Application for Explosives Decontamination
Authors: Ying Yulong , Plutnar Jan , Pumera Martin 
Published: May 2021

AbstractMicro/nanomotors are capable of a wide variety of tasks related, i.e., to biomedical or environmental applications. Light‐driven semiconductor‐based micromotors are especially appealing, as they can split surrounding water via light irradiation, and therefore, they can move infinitely. However, their motion is typically limited to in‐plane motion with four degrees of freedom (4DoF) or even pseudo‐1D motion with 2DoF. Herein, magnetically steerable tubular TiO2/Fe3O4/CdS micromotors, termed microsubmarines, with 6DoF motion, based on a fuel‐free design where surrounding water acts as fuel upon visible light irradiation, are presented, with an average velocity of 7.9 µm s−1. Besides, the generation of radicals via such water splitting aids the photocatalytic chemicals degradation with the potential to use solar radiation. A light‐induced self‐electrophoretic mechanism is responsible for the self‐propulsion and can be used to predict the motion direction based on the structure and composition. Finally, the TiO2/Fe3O4/CdS microsubmarines are tested in a proof‐of‐concept application of high‐energy explosive, e.g., picric acid, photocatalytic degradation, with the best performance owing to the versatility of 6DoF motion, the surface coating with amorphous TiO2 layer, and UV light. The results can help optimize light‐active micromotor design for potential national security and environmental application, hydrogen evolution, and target cargo delivery.
Investigation on methanol–gasoline–aluminum oxyhydroxide nanoparticle blends on the emission characteristics of an SI engine
Authors: Aravind A. , Saravanan S. , Bhavin K. Bharath , Arul Mozhi Selvan V. 
Published: May 2021

AbstractExperiments were carried out to reduce the harmful exhaust emissions from the engine through various in‐cylinder techniques such as nanoparticles blended fuel. In this present investigation, the effect of methanol‐gasoline fuel blends (M10, M30, and M50) and neat gasoline (G100) on a single‐cylinder four‐stroke SI engine was studied under idle throttle operating conditions to obtain the characteristics of total fuel consumption and exhaust emissions. The fuel‐borne nanoparticles such as aluminum oxyhydroxide [AlO(OH)] from 50 to 150 ppm were mixed with methanol gasoline blends. AlO(OH) behaves like a fire retardant which prevents detonation and knocking under a higher concentration of methanol gasoline blends. The SI engine was running without any problem using gasoline–methanol blends up to M50 under idling and acceleration. However, the engine was running under idling conditions using neat methanol (M100) and failed to run under acceleration due to poor combustion under a rich mixture. The total fuel consumption decreased with the use of methanol and significant reductions were observed on engine surface temperature, exhaust gas temperature, and the exhaust emissions such as carbon monoxide, hydrocarbons, and nitrogen oxide when compared with neat gasoline.
Practices, challenges, and opportunities when addressing the palliative care needs of people living with dementia: Specialty memory care provider perspectives
Authors: Bernstein Sideman Alissa , Harrison Krista L. , Garrett Sarah B. , Naasan Georges ,   Dementia Palliative Care Writing Group, Ritchie Christine S. 
Published: May 2021

AbstractIntroductionPalliative care focuses on reducing suffering and improving quality of life for individuals with serious illness and their families. In an effort to develop palliative care interventions for specialty memory care clinics, this study characterizes memory care providers’ perspectives on addressing palliative care needs of people living with dementia (PLWD).MethodsQualitative interviews with specialty memory care providers were followed by thematic analysis by a multidisciplinary research team.ResultsProvider approaches overlap with key domains of palliative care. Approaches unique to dementia include having a detailed understanding of dementia syndromes, behavioral symptoms, and caregiver burden. Challenges were identified related to disease progression, provider‐level factors, and systems and cultural issues. Respondents identified training needed to strengthen a palliative care approach.DiscussionThere are many strengths of using memory care teams to address palliative care needs of PLWD. However, they may require additional knowledge and training to strengthen their work.