bluuebunny/crossref_metadata_2025 huggingface dataset:
Homology‐ and cross‐resistance of Lactobacillus plantarum to acid and osmotic stress and the influence of induction conditions on its proliferation by RNA‐Seq
Authors: Wu Jingyi , Yan Xu , Weng Peifang , Chen Gong , Wu Zufang
Published: May 2021

In this study, homology‐ and cross‐resistance of Lactobacillus plantarum L1 and Lactobacillus plantarum L2 to acid and osmotic stress were investigated. Meanwhile, its proliferation mechanism was demonstrated by transcriptomic analysis using RNA sequencing. We found that the homologous‐resistance and cross‐resistance of L. plantarum L1 and L. plantarum L2 increased after acid and osmotic induction treatment by lactic acid and sodium lactate solution in advance, and the survival rate of live bacteria was improved. In addition, the count of viable bacteria of L. plantarum L2 significantly increased cultivated at a pH 5.0 with a 15% sodium lactate sublethal treatment, compared with the control group. Further study revealed that genes related to membrane transport, amino acid metabolism, nucleotide metabolism, and cell growth were significantly upregulated. These findings will contribute to promote high‐density cell culture of starter cultures production in the fermented food industry.
Asian meteorological droughts on three time scales and different roles of sea surface temperature and soil moisture
Authors: Zhang Yanting , Wu Renguang
Published: May 2021

The present study utilizes the standard precipitation index (SPI) to differentiate Asian summer droughts that are associated with variations of precipitation over periods of 3, 9 and 24 months (termed as short‐term, medium‐term and long‐term droughts, respectively). Then, the relationships between these droughts and atmospheric circulation, sea surface temperature (SST), and soil moisture are investigated. While the spatial and temporal characteristics of short‐term and medium‐term droughts are fairly similar, long‐term droughts display different spatial and temporal features. The leading spatial mode of short‐term and medium‐term droughts exhibits a dipole pattern with opposite loading north and south of approximately 30°N. The second spatial mode displays a tripole pattern with the same sign of loading over India and north‐northeast China–Mongolia and opposite loading in between. Temporal variations of short‐term and medium‐term droughts are dominated by interannual variabilities. For long‐term droughts, the first two spatial modes switch their order, and the long‐term trends are as important as the interannual and interdecadal variabilities. The droughts of the dipole mode are associated with SST anomalies featuring an El Niño‐like pattern in the tropical Indo‐Pacific Ocean that affect the drought variations through inducing large‐scale divergence and convergence. The interannual variability of the droughts with the dipole mode is also associated with the SST anomalies in the North Atlantic Ocean that affect the North Atlantic‐Eurasian atmospheric circulation. Local soil moisture conditions are more important for the formation of long‐term droughts than short‐term and medium‐term droughts.
Advanced training enhances readiness to return to sport after anterior cruciate ligament reconstruction
Authors: Meierbachtol Adam , Obermeier Michael , Yungtum William , Bottoms John , Paur Eric , Nelson Bradley J. , Tompkins Marc , Chmielewski Terese L.
Published: May 2021

Patients with anterior cruciate ligament reconstruction (ACLR) are often psychologically and physically under‐prepared for sports participation. This study compared readiness to return to sport based on completion of advanced training after ACLR. Patients with ACLR who self‐selected participation in a 6‐week group‐format advanced training program (TRAINING) were compared to age‐ and sex‐matched patients who did not participate (NoTRAINING). Each group had 23 participants (14 females). Advanced training consisted of plyometric, strengthening, and agility exercises. Baseline and follow‐up testing included psychological measures (Anterior Cruciate Ligament Return to Sport after Injury [ACL‐RSI]; Tampa Scale for Kinesiophobia [TSK‐11]; Knee Activity Self‐Efficacy [KASE]; and fear intensity for the primary fear‐evoking task or situation) and a hop test battery. Return to sport criteria were ACL‐RSI score ≥70 points and limb symmetry index ≥90% on all hop tests. At follow‐up, KASE score was higher in TRAINING than NoTRAINING (92.7 vs. 89.1 points; respectively), but ACL‐RSI, TSK‐11 and fear intensity scores were not significantly different between groups. Return to sport criteria passing rate was not significantly different between groups at baseline (TRAINING: 13%, NoTRAINING: 30%) or follow‐up (TRAINING: 52%, NoTRAINING: 43%); however, the distribution of criteria met at follow‐up differed with more patients in TRAINING than NoTRAINING meeting hop test criteria (30% vs. 4%, respectively) and more patients in NoTRAINING than TRAINING failing to meet any criteria (25% vs. 0%, respectively). Advanced training after ACLR facilitated readiness for sport participation by improving confidence and hop performance, but may not have a preferential effect on fear.
Unique ion filter—A data reduction tool for chemometric analysis of raw comprehensive two‐dimensional gas chromatography‐mass spectrometry data
Authors: Adutwum Lawrence A. , Kwao Joanna Koryo , Harynuk James J.
Published: May 2021

Comprehensive gas chromatography with time of flight mass spectrometry is a powerful tool in the analysis of complex samples. Chemometric analysis of raw chromatographic data is more useful in one‐ and two‐dimensional separations relative to peak tables. The data volume from such experiments generally necessitates the use of data reduction tools. Such tools often sacrifice some of the multivariate information in the mass to charge ratio dimension. The unique ion filter reduces the over‐redundancy in two‐dimensional gas chromatography‐mass spectrometry data by limiting the data to a few unique/pseudo‐unique ions, sub‐peaks/slices in the first dimension, and spectra in the second dimension. We explore the performance of this algorithm through careful inspection of two‐dimensional gas chromatography‐mass spectrometry data before and after application of the filter. A reduction (99%) in the number of variables in a two‐dimensional gas chromatography‐mass spectrometry chromatogram passed on to subsequent analysis was observed. Feature selection times for model optimization reduced from 229 (±13) to 6.8 (±0.5) min when the filter was applied. An estimate of two unique/pseudo‐unique ions, one sub‐peak in the first dimension and five spectra in the second dimension were considered to provide a true representation of each chromatogram and provided enough information to achieve 100% model prediction accuracy.
Prochlorococcus,Synechococcus, and picoeukaryotic phytoplankton abundances in the global ocean
Authors: Visintini Natalia , Martiny Adam C. , Flombaum Pedro
Published: May 2021

Marine picophytoplankton is the most abundant photosynthetic group on Earth; however, it is still underrepresented in dynamic ecosystem models. Major constraints for understanding its role in the ecosystem at a global scale are sparse data and lack of a baseline description of its distribution. Here, we present three datasets to assess the global abundance of the principal groups of picophytoplankton,Prochlorococcus,Synechococcus, and picoeukaryotic phytoplankton: (1) a compilation of 109,045 field observations with ancillary environmental data, (2) a global monthly climatology of 1° grids from 0 to 200 m, and (3) four climate scenarios projections, from the Coupled Model Intercomparison Project 5, spanning years 1901 to 2100. Together this set of observational and modeled data can improve our understanding of the role of picophytoplankton in the global ecosystem.
Low‐Threshold Lasing from Copper‐Doped CdSe Colloidal Quantum Wells
Authors: Yu Junhong , Sharma Manoj , Li Mingjie , Delikanli Savas , Sharma Ashma , Taimoor Muhammad , Altintas Yemliha , McBride James R. , Kusserow Thomas , Sum Tze‐Chien , Demir Hilmi Volkan , Dang Cuong
Published: May 2021

Transition metal doped colloidal nanomaterials (TMDCNMs) have recently attracted attention as promising nano‐emitters due to dopant‐induced properties. However, despite ample investigations on the steady‐state and dynamic spectroscopy of TMDCNMs, experimental understandings of their performance in stimulated emission regimes are still elusive. Here, the optical gain properties of copper‐doped CdSe colloidal quantum wells (CQWs) are systemically studied with a wide range of dopant concentration for the first time. This work demonstrates that the amplified spontaneous emission (ASE) threshold in copper‐doped CQWs is a competing result between the biexciton formation, which is preferred to achieve population inversion, and the hole trapping which stymies the population inversion. An optimum amount of copper dopants enables the lowest ASE threshold of ≈7 µJ cm−2, about 8‐fold reduction from that in undoped CQWs (≈58 µJ cm−2) under sub‐nanosecond pulse excitation. Finally, a copper‐doped CQW film embedded in a vertical cavity surface‐emitting laser (VCSEL) structure yields an ultralow lasing threshold of 4.1 µJ cm−2. Exploiting optical gain from TMDCNMs may help to further boost the performance of colloidal‐based lasers.
Quantification of Triple‐Shape Memory Behavior of Polymers Utilizing Tension and Torsion
Authors: Meurer Josefine , Rodriguez Agudo José Alberto , Zechel Stefan , Hager Martin D. , Schubert Ulrich S.
Published: May 2021

Shape‐memory polymers (SMPs) are well investigated smart materials. With their ability to memorize their original shape they are interesting candidates for a large range of applications. Certain SMPs feature triple shape‐memory behavior. In these cases, it is possible to fix two different temporary shapes. However, the exact quantification of the individual steps regarding their programming and recovery rate is difficult and has not been possible so far. In this work, a novel approach for the analysis and exact quantification of triple SMPs is presented. By applying a customized rheology protocol, it is possible to perform and to analyze torsional and tensional experiments simultaneously. Consequently, different shapes in different directions (vertical and horizontal) can be fixed and the individual steps can be investigated independently at different switching temperatures.
Staphylococcus aureusST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence
Authors: Bongiorno Dafne , Musso Nicolò , Caruso Giuseppe , Lazzaro Lorenzo Mattia , Caraci Filippo , Stefani Stefania , Campanile Floriana
Published: May 2021

The ability ofS. aureusto infect bone and osteoblasts is correlated with its incredible virulencearmamentariumthat can mediate the invasion/internalization process, cytotoxicity, membrane damage, and intracellular persistence. We comparatively analyzed the interaction, persistence, and modulation of expression of selected genes and cell viability in an ex vivo model using human MG‐63 osteoblasts of two previously studied and well‐characterizedS. aureusclinical strains belonging to the ST239‐SCCmecIII‐t037 and ST228‐SCCmecI‐t041 clones at 3 h and 24 h post‐infection (p.i).S. aureusATCC12598 ST30‐t076 was used as a control strain. Using imaging flow cytometry (IFC), we found that these strains invaded and persisted in MG‐63 osteoblasts to different extents. The invasion was evaluated at 3 h p.i and persistence at 24 h p.i., in particular: ATCC12598 internalized in 70% and persisted in 50% of MG‐63 cells; ST239‐SCCmecIII internalized in 50% and persisted in 45% of MG‐63 cells; and ST228‐SCCmecI internalized in 30% and persisted in 20% of MG‐63 cells. During the infection period, ST239‐III exerted significant cytotoxic activity resulting from overexpression ofhlaandpsmA and increased expression of the genes involved in adhesion, probably due to the release and re‐entry of bacteria inside MG‐63 cells at 24 h p.i. The lower invasiveness of ST228‐I was also associated with non‐cytotoxic activity inside osteoblasts. This clone was unable to activate sufficient cellular reaction and succumbed inside MG‐63 cells. Our findings support the idea of considering new strategies, based on a translational approach—eukaryotic host–pathogen interaction (EHPI)—and to be applied on a large scale, to predictS. aureus/osteoblast interaction and treat bone infections. Such strategies rely on the study of the genetic and biochemical basis of both pathogen and host.
A study of the fractal foam drainage model in a microgravity space
Authors: Wang Kang‐Le
Published: May 2021

The foam drainage mainly depends on the influence of gravity and foam surface tension. In this work, we consider the foam drainage in a microgravity condition, and its fractal modification is established by using the fractal derivative. The variational principle of the novel fractal model is successfully obtained by the semi‐inverse method. Finally, an analytical solution is obtained by the variational iteration method; the effect of the fractal order on the solution property is illustrated.
Technical Note: Volumetric coverage in breast tomosynthesis images — Phantom QC results from the TMIST study
Authors: Maki Aili K. , Mainprize James G. , Pisano Etta D. , Mawdsley Gordon E. , Skarpathiotakis Mia , Yaffe Martin J.
Published: May 2021

Purpose

In the reconstruction of volume breast images from x‐ray projections in breast tomosynthesis, some tomographic systems truncate the image data presented to the radiologist such that a non‐negligible amount of tissue may be missing from the breast image. QC tests were conducted to determine if this problem existed in imaging in the TMIST study.

Methods

Test tools developed for TMIST containing small objects at known heights were used in routine weekly and annual QC testing of tomosynthesis units to assess the degree to which phantom material that was irradiated in imaging was excluded from the reconstructed image. Results from 318 tests on five system types from three manufacturers are reported.

Results

The presence and extent of this problem varied among system types. The cause was most frequently related to machine errors in the determination of breast thickness or to deflection of components during breast compression. In particular, the problem occurred when a compression paddle other than the one calibrated for tomosynthesis was used for the tests. This was also verified to have occurred in some clinical imaging.

Conclusions

Missing volume can be avoided by intentionally reconstructing additional image slices above and below the presumed locations of the breast support and compression plate. A compression paddle which has been calibrated for tomosynthesis should be used both for clinical imaging and testing. The prevalence of this phenomenon suggests that more frequent testing for volume coverage may be advisable.
Is coronavirus disease 2019 associated with indicators of long‐term bladder dysfunction?
Authors: Welk Blayne , Richard Lucie , Braschi Emmanuel , Averbeck Marcio A
Published: May 2021

Objective

Early reports have suggested that coronavirus disease 2019 (COVID‐19) can present with significant urinary frequency and nocturia, and that these symptoms correlate with markers of inflammation in the urine. We evaluated surrogate markers of chronic urinary symptoms to determine if they were more frequent after COVID‐19 infection.

Methods

Routinely collected data from the province of Ontario was used to conduct a matched, retrospective cohort study. We identified patients 66 years of age or older who had a positive COVID‐19 test between February and May 2020 and survived at least 2 months after their diagnosis. We matched them to two similar patients who did not have a positive COVID‐19 test during the same time period. We measured the frequency of urology consultation, cystoscopy, and new prescriptions for overactive bladder medications during a subsequent 3‐month period. Proportional hazard models were adjusted for any baseline differences between the groups.

Results

We matched 5617 patients with COVID‐19 to 11,225 people who did not have COVID‐19. The groups were similar, aside from a higher proportion of patients having hypertension and diabetes in the CoVID‐19 cohort. There was no significantly increased hazard of new receipt of overactive bladder medication (hazards ratio [HR]: 1.04, p = 0.88), urology consultation (HR: 1.40, p = 0.10), or cystoscopy (HR: 1.14, p = 0.50) among patients who had COVID‐19, compared to the matched cohort.

Conclusion

Surrogate markers of potential bladder dysfunction were not significantly increased in the 2–5 months after COVID‐19 infection.
Performance analysis of integrated RF microstrip transmit antenna arrays with high channel count for body imaging at 7 T
Authors: Fiedler Thomas M. , Orzada Stephan , Flöser Martina , Rietsch Stefan H. G. , Quick Harald H. , Ladd Mark E. , Bitz Andreas K.
Published: May 2021

The aim of the current study was to investigate the performance of integrated RF transmit arrays with high channel count consisting of meander microstrip antennas for body imaging at 7 T and to optimize the position and number of transmit elements. RF simulations using multiring antenna arrays placed behind the bore liner were performed for realistic exposure conditions for body imaging. Simulations were performed for arrays with as few as eight elements and for arrays with high channel counts of up to 48 elements. The B1+ field was evaluated regarding the degrees of freedom for RF shimming in the abdomen. Worst‐case specific absorption rate (SARwc), SAR overestimation in the matrix compression, the number of virtual observation points (VOPs) and SAR efficiency were evaluated. Constrained RF shimming was performed in differently oriented regions of interest in the body, and the deviation from a target B1+ field was evaluated. Results show that integrated multiring arrays are able to generate homogeneous B1+ field distributions for large FOVs, especially for coronal/sagittal slices, and thus enable body imaging at 7 T with a clinical workflow; however, a low duty cycle or a high SAR is required to achieve homogeneous B1+ distributions and to exploit the full potential. In conclusion, integrated arrays allow for high element counts that have high degrees of freedom for the pulse optimization but also produce high SARwc, which reduces the SAR accuracy in the VOP compression for low‐SAR protocols, leading to a potential reduction in array performance. Smaller SAR overestimations can increase SAR accuracy, but lead to a high number of VOPs, which increases the computational cost for VOP evaluation and makes online SAR monitoring or pulse optimization challenging. Arrays with interleaved rings showed the best results in the study.
Work environment for hospital nurses in Japan: The relationships between nurses' perceptions of their work environment and nursing outcomes
Authors: Ogata Yasuko , Sato Kana , Kodama Yoshimi , Morioka Noriko , Taketomi Kikuko , Yonekura Yuki , Katsuyama Kimiko , Tanaka Sachiko , Nagano Midori , Ito Yoichi M. , Kanda Katsuya ,   the rest of the WENS‐J project team
Published: May 2021

Aim

To investigate nurses' perceptions of their work environment and to investigate the relationships between variables measuring the work environment (WE) and nursing outcomes (NOs).

Design

A 2‐year prospective longitudinal survey (2013–2015).

Method(s)

Descriptive statistics of nurse demographics, organizational WE and NOs were calculated by position. The associations between Practice Environment Scale of the Nursing Work Index (PES‐NWI) and NOs were examined for each unit.

Results

The participants were 2,992 staff nurses, 137 nurse managers (NMs), and 8 chief nursing officers in Phase 1 and 7,849, 371 and 23 in Phase 2, respectively. The higher the job position, the better the WE was rated. The higher the PES‐NWI scores, the better the outcomes. Descriptive statistics about organizational WEs and NOs and the statistically significant associations between the two were identified.
Experiences of nurses caring for perinatal women and newborns during the COVID‐19 pandemic: A descriptive qualitative study
Authors: Kang Hee Sun , Son Yedong , Kim Mi Ja , Chae Sun‐Mi
Published: May 2021

Aim

Nurses are pivotal in caring for patients infected with COVID‐19. Little is known about experiences of nurses in maternity care during the pandemic. Therefore, this study aimed to describe nurses’ experiences of caring for perinatal women and newborns during the pandemic.

Design

A descriptive qualitative study was conducted.

Methods

Data were collected from August–November 2020 using focus group and in‐depth interviews. A total of 24 nurses working in maternity and newborn care units participated in the study. Content analysis method was used for data analysis.

Results

The participants’ clinical experience ranged from 6 months–26 years. Three major themes emerged as follows: “making every effort to prevent COVID‐19 infection,” “caring for perinatal women and newborns with COVID‐19 infection or suspected infection” and “job stress and professional growth during the pandemic.” Participants reported that they needed more support in terms of staffing and mental health.
Product Control and Insight into Conversion of C6 Aldose Toward C2, C4 and C6 Alditols in One‐Pot Retro‐Aldol Condensation and Hydrogenation Processes
Authors: Hui Yingshuang , Zhan Yulu , Hou Wenrong , Gao Lou , Zhang Yahong , Tang Yi
Published: May 2021

Alcohols have a wide range of applicability, and their functions vary with the carbon numbers. C6 and C4 alditols are alternative of sweetener, as well as significant pharmaceutical and chemical intermediates, which are mainly obtained through the fermentation of microorganism currently. Similarly, as a bulk chemical, C2 alditol plays a decisive role in chemical synthesis. However, among them, few works have been focused on the chemical production of C4 alditol yet due to its difficult accumulation. In this paper, under a static and semi‐flowing procedure, we have achieved the product control during the conversion of C6 aldose toward C6 alditol, C4 alditol and C2 alditol, respectively. About C4 alditol yield of 20 % and C4 plus C6 alditols yield of 60 % are acquired in the one‐pot conversion via a cascade retro‐aldol condensation and hydrogenation process. Furthermore, in the semi‐flowing condition, the yield of ethylene glycol is up to 73 % thanks to its low instantaneous concentration.
Omeg@Silica: Entrapment and Stabilization of Sustainably Sourced Fish Oil
Authors: Ciriminna Rosaria , Lino Claudia , Pagliaro Mario
Published: May 2021

Fish oil rich in long‐chain polyunsaturated fatty acids, vitamin D3 and carotenoid pigments have been sustainably extracted from anchovy fillet leftovers using biobased limonene. The oil is conveniently stabilized by adsorption on periodic mesoporous silicas. The simplicity of the process, the high load of fish oil, and the biocompatible nature of mesoporous silica support numerous forthcoming applications of this new class of “Omeg@Silica” materials.
Recovery and Reuse of Composite Cathode Binder in Lithium Ion Batteries
Authors: Sarkar Amrita , May Richard , Ramesh Sapna , Chang Wesley , Marbella Lauren E.
Published: May 2021

Here, we investigate the recovery and reuse of polyvinylidene fluoride (PVDF) binders from both homemade and commercial cathode films in Li ion batteries. We find that PVDF solubility depends on whether the polymer is an isolated powder or cast into a composite film. A mixture of tetrahydrofuran:N‐methyl‐2‐pyrrolidone (THF : NMP, 50 : 50 v/v) at 90 °C delaminates composite cathodes from Al current collectors and yields pure PVDF as characterized by 1H nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), wide‐angle X‐ray scattering (WAXS), and scanning electron microscopy (SEM). PVDF recovered from Li ion cells post‐cycling exhibits similar performance to pristine PVDF. These data suggest that PVDF can be extracted and reused during Li ion battery recycling while simultaneously eliminating the formation of HF etchants, providing an incentive for use in direct cathode recycling.
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

Primary 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

The 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

Purpose

Understanding 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.

Methods

An 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.

Results

A 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.

Conclusions

These 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

Angiotensin 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

While 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

Evidence 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

Model‐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

The 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

Background

CAPARFI 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.

Methods

Twenty 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.

Results

Acoustic 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).

Conclusions

This 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

Osimertinib 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

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

Micro/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

Experiments 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

Introduction

Palliative 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).

Methods

Qualitative interviews with specialty memory care providers were followed by thematic analysis by a multidisciplinary research team.

Results

Provider 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.

Discussion

There 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.