bluuebunny/crossref_metadata_2025 huggingface dataset:
ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice
Authors: Yu Ting , Ling Qiao , Xu Mengxin , Wang Niu , Wang Lixia , Lin Hanwen , Cao Manqi , Ma Yong , Wang Yuanyuan , Li Kuibiao , Du Liubing , Jin Yunyun , Li Ying , Guo Deyin , Peng Xiaoxue , Chen Yao‐qing , Zhao Bo , Pan Ji‐An
Published: May 2022

As one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N‐terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum‐Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID‐19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail‐vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle‐ and ORF8‐treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5‐week‐old male mice. Furthermore, the analysis of gene expression in the testes between vehicle‐ and ORF8‐treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection on the human reproductive system.
Long‐term evolution of cold air pools over the Madrid basin
Authors: Rasilla Domingo F. , Martilli Alberto , Allende Fernando , Fernández Felipe
Published: May 2022

Cold air pools (CAPs) are one of the most severe weather conditions experienced across many basins worldwide, related to episodes of extreme cold temperatures, poor air quality, and disruption of transportation networks. This study offers a basic climatology of CAPs in the southern Spanish Plateau and investigates its evolution since 1961 and their links with local, synoptic, and large‐scale climate variability. It is based on the comparison of meteorological records from two stations, one in the Sistema Central Range (Navacerrada, 1,894 m asl) and another at the plain (Madrid‐Barajas, 609 m asl). Accuracy and representativeness of both locations to depict the spatial and temporal variability of CAPs was also tested. CAPs days (defined as the simultaneous occurrence of a daily minimum temperature difference above 0.1°C between both stations) were found to occur year‐round, but the most frequent and intense occur in winter (NDJ). Some typical features of CAPs, such as local mesoscale processes (katabatic and anabatic flows) in connection with synoptic (advection of mid‐troposphere warm air masses during high‐pressure regimes) and hemispheric (a positive phase of the North Atlantic Oscillation) variability were also observed, leading to a sheltered boundary layer at the bottom of southern Spanish Plateau, decoupled from the free troposphere. By night, CAPs have maintained both their frequency and intensity, which means that the frequency of extremely cold nights on the plain has remained relatively stable (despite global warming). By day, an enhanced warming of the high‐elevation site has increased the temperature difference between the mountains and the plain during CAP days.
Changes in the frequency and temperature of air masses over east‐central Europe
Authors: Bartoszek Krzysztof , Kaszewski Bogusław M.
Published: May 2022

The study specifies the circulation conditions, the frequency of occurrence, long‐term changes, and thermal characteristics of air masses over east‐central Europe in the years 1951–2020. The division of air masses utilized by The Polish Institute of Meteorology and Water Management was used, where, based on the geographical location of the source areas, Arctic (A), Polar maritime fresh (mPf), Polar maritime old (transformed) (mPo), Polar maritime warm (mPw), Polar continental (cP), and Tropical (T) air masses are distinguished. It has been shown that western circulation dominates in this area (60% of days on average), during which the advection of maritime air masses occurs. The share of Arctic air mass flowing from the north (about 12% of days a year) and Tropical air mass from the southern sector (4% of days) is clearly smaller. The results of the research have shown that the frequency of the majority of the analysed air masses was subject to short‐term changes in the studied period. On the other hand, long‐term changes in this frequency concerned two air masses flowing from lower latitudes (mPw and T). In the case of mPw, in the period 1951–2020 there was a significant increase in frequency, not only on a yearly basis, but also in all seasons. In the last two decades, the frequency of Tropical air mass has also increased significantly, while the increase took place only in the summer period. Therefore, the increase in air temperature recorded in east‐central Europe since the 1990s, mainly in the warm half of the year, should to a large extent be attributed to both the greater frequency of the inflow of air masses from lower latitudes (mPw and T) and the increase in temperature in virtually all separated air masses, which in turn is a result of progressing global warming.
Analysis of requirements for developing a mobile device‐based medicines management application for people who are blind and visually impaired
Authors: Dinari Fatemeh , Bahaadinbeigy Kambiz , Moulaei Khadijeh
Published: May 2022

Background

People with visual impairments are often faced with challenges in the process of medicines management and use. Mobile device‐based applications can be a potential solution in reducing these challenges.

Objectives

This study aimed to analyse the requirements for developing a mobile device‐based medicines management application for people who are blind and visually impaired.

Methods

A questionnaire was designed to examine the requirements for developing a medicines management application for people who were blind and visually impaired. The questionnaire was sent to 2081 people who are blind or visually impaired, and their instructors. Among them, 146 people (125 with visual impairments and 21 instructors) completed the questionnaire. SPSS 23 software was used for statistical analysis.

Results

Ninety percent of people with visual impairments and 75% of instructors were willing to assist in application design. Out of 44 data elements, 35 were considered important for designing and creating mobile device‐based medicines management applications. ‘Providing education information about drugs in the form of audio files’ (4.71 ± 0.56), ‘Ability to update software’ (4.71 ± 0.56) and ‘Ability to search for physician’s addresses’ (4.71 ± 0.46) were rated highest, in terms of required ‘Application capabilities’, by the study cohort based on average Likert scale scores (1 = very low, 2 = low, 3 = moderate, 4 = high, 5 = very high).

Conclusion

This study provides a set of data elements that people who are blind and visually impaired, and their instructors, have identified as being important to the development and design of mobile device‐based medicines management applications. Developers can use the identified data elements to help in the design and implementation of their medicines management applications or electronic systems. Applications and electronic systems that incorporate features for people who are blind and visually impaired, have the potential to improve quality of life by enabling independent medicines management and medicines adherence, whilst potentially decreasing medication errors, rate of diseases, frequency of hospitalisations and medicines related deaths.
A Deep Learning Model for Classification of Parotid Neoplasms Based on Multimodal Magnetic Resonance Image Sequences
Authors: Liu Xu , Pan Yucheng , Zhang Xin , Sha Yongfang , Wang Shihui , Li Hongzhe , Liu Jianping
Published: May 2022

Objective

To design a deep learning model based on multimodal magnetic resonance image (MRI) sequences for automatic parotid neoplasm classification, and to improve the diagnostic decision‐making in clinical settings.

Methods

First, multimodal MRI sequences were collected from 266 patients with parotid neoplasms, and an artificial intelligence (AI)‐based deep learning model was designed from scratch, combining the image classification network of Resnet and the Transformer network of Natural language processing. Second, the effectiveness of the deep learning model was improved through the multi‐modality fusion of MRI sequences, and the fusion strategy of various MRI sequences was optimized. In addition, we compared the effectiveness of the model in the parotid neoplasm classification with experienced radiologists.

Results

The deep learning model delivered reliable outcomes in differentiating benign and malignant parotid neoplasms. The model, which was trained by the fusion of T2‐weighted, postcontrast T1‐weighted, and diffusion‐weighted imaging (b = 1000 s/mm2), produced the best result, with an accuracy score of 0.85, an area under the receiver operator characteristic (ROC) curve of 0.96, a sensitivity score of 0.90, and a specificity score of 0.84. In addition, the multi‐modal paradigm exhibited reliable outcomes in diagnosing the pleomorphic adenoma and the Warthin tumor, but not in the identification of the basal cell adenoma.

Conclusion

An accurate and efficient AI based classification model was produced to classify parotid neoplasms, resulting from the fusion of multimodal MRI sequences. The effectiveness certainly outperformed the model with single MRI images or single MRI sequences as input, and potentially, experienced radiologists.

Level of Evidence

3 Laryngoscope, 133:327–335, 2023
Bisurfactant‐functionalized TiO2 nanoparticles as additives of the lubricating oil
Authors: Ma Hongxia , Wu Wei , Wang Zeyun
Published: May 2022

In this work, TiO2 nanoparticles modified with octadecylamine and dodecyl mercaptan (DDM/ODA@PDA@TiO2 NPs) are uesd to improve the tribological properties of the white oil. The DDM/ODA@PDA@TiO2 NPs which are simply prepared by mussel inspired chemistry and the Michael addition reaction can be facilely dispersed in the white base oil. Tribological measurements showed that the dispersion of the white oil containing 3 wt% DDM/ODA@PDA@TiO2 NPs displays significant reductions in the friction coefficient and wear scar diameter at room temperature and 75°C. Further XPS investigation shows that the favourable tribological properties of DDM/ODA@PDA@TiO2 NPs are ascribed to the synergistic effect of tribofilm (Fe2O3, Fe3O4, FeS2, FeS and FeSO4) and TiO2 nanofluids.
CAQ Corner: Surgical evaluation for liver transplantation
Authors: Misra Asish C. , Emamaullee Juliet
Published: May 2022

The evaluation of a liver transplantation candidate is a complex and detailed process that in many cases must be done in an expedited manner because of the critically ill status of some patients with end‐stage liver disease. It involves great effort from and the collaboration of multiple disciplines, and during the evaluation several studies and interventions are performed to assess and potentially prepare a patient for liver transplant. Here we review the liver transplantation evaluation from a surgical perspective.
Characterization and microsatellite marker development for a common bark and ambrosia beetle associate, Geosmithia obscura
Authors: Pietsch Grace M. , Gazis Romina , Klingeman William E. , Huff Matthew L. , Staton Margaret E. , Kolarik Miroslav , Hadziabdic Denita
Published: May 2022

Symbioses between Geosmithia fungi and wood‐boring and bark beetles seldom result in disease induction within the plant host. Yet, exceptions exist such as Geosmithia morbida, the causal agent of Thousand Cankers Disease (TCD) of walnuts and wingnuts, and Geosmithia sp. 41, the causal agent of Foamy Bark Canker disease of oaks. Isolates of G. obscura were recovered from black walnut trees in eastern Tennessee and at least one isolate induced cankers following artificial inoculation. Due to the putative pathogenicity and lack of recovery of G. obscura from natural lesions, a molecular diagnostic screening tool was developed using microsatellite markers mined from the G. obscura genome. A total of 3256 candidate microsatellite markers were identified (2236, 789, 137 di‐, tri‐, and tetranucleotide motifs, respectively), with 2011, 703, 101 di‐, tri‐, and tetranucleotide motifs, respectively, containing markers with primers. From these, 75 microsatellite markers were randomly selected, screened, and optimized, resulting in 28 polymorphic markers that yielded single, consistently recovered bands, which were used in downstream analyses. Five of these microsatellite markers were found to be specific to G. obscura and did not cross‐amplify into other, closely related species. Although the remaining tested markers could be useful, they cross‐amplified within different Geosmithia species, making them not reliable for G. obscura detection. Five novel microsatellite markers (GOBS9, GOBS10, GOBS41, GOBS43, and GOBS50) were developed based on the G. obscura genome. These species‐specific microsatellite markers are available as a tool for use in molecular diagnostics and can assist future surveillance studies.
Seasonal phytoplankton and geochemical shifts in the subsurface chlorophyll maximum layer of a dimictic ferruginous lake
Authors: Swanner Elizabeth D. , Wüstner Marina , Leung Tania , Pust Jürgen , Fatka Micah , Lambrecht Nick , Chmiel Hannah E. , Strauss Harald
Published: May 2022

Subsurface chlorophyll maxima layers (SCML) are ubiquitous features of stratified aquatic systems. Availability of the micronutrient iron is known to influence marine SCML, but iron has not been explored in detail as a factor in the development of freshwater SCML. This study investigates the relationship between dissolved iron and the SCML within the dimictic, ferruginous lake Grosses Heiliges Meer in northern Germany. The occurrence of the SCML under nonferruginous conditions in the spring and ferruginous conditions in the fall are context to explore temporal changes in the phytoplankton community and indicators of primary productivity. Results indicate that despite more abundant chlorophyll in the spring, the SCML sits below a likely primary productivity maximum within the epilimnion, inferred based on colocated dissolved oxygen, δ13CDIC, and pH maxima. The peak amount of chlorophyll in the SCML is lower in the fall than in the spring, but in the fall the SCML is colocated with elevated dissolved iron concentrations and a local δ13CDICmaximum. Cyanobacteria and Chlorophyta have elevated abundances within the SCML in the fall. Further investigation of the relationship of iron to primary productivity within ferruginous SCML may help to understand the environmental controls on primary productivity in past ferruginous oceans.
Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery
Authors: Song Yihui , Yang Xinyu , Wang Shu , Zhao Min , Yu Bin
Published: May 2022

The protein tyrosine phosphatase SHP2 encoded by PTPN11 is a promising therapeutic target for cancer therapy. The dynamic change of SHP2 between closed and open conformations under either physiological or pathological conditions provides opportunities to design SHP2 inhibitors for treating SHP2‐related diseases. To date, several SHP2 allosteric inhibitors have advanced into clinical trials as mono‐ or combined therapy of cancers. In this review, we provide an overview on the structural landscape of SHP2 under physiological and pathological conditions and also comprehensively analyze the binding models of SHP2/inhibitor complexes. Structural features of SHP2 under pathological conditions and co‐crystal structures of SHP2/inhibitor complexes will definitely facilitate structure‐guided design of SHP2 inhibitors. Finally, proteolysis targeting chimeric (PROTAC) based SHP2 degraders have shown therapeutic promise for cancer therapy and are also briefly discussed. We hope this review could provide crystallographic landscape for SHP2 targeted drug discovery.
Small‐molecule inhibitors of cyclophilin D as potential therapeutics in mitochondria‐related diseases
Authors: Haleckova Annamaria , Benek Ondrej , Zemanová Lucie , Dolezal Rafael , Musilek Kamil
Published: May 2022

Cyclophilin D (CypD) is a key regulator of mitochondrial permeability transition pore (mPTP) opening. This pathophysiological phenomenon is associated with the development of several human diseases, including ischemia‐reperfusion injury and neurodegeneration. Blocking mPTP opening through CypD inhibition could be a novel and promising therapeutic approach for these conditions. While numerous CypD inhibitors have been discovered to date, none have been introduced into clinical practice, mostly owing to their high toxicity, unfavorable pharmacokinetics, and low selectivity for CypD over other cyclophilins. This review summarizes current knowledge of CypD inhibitors, with a particular focus on small‐molecule compounds with regard to their in vitro activity, their selectivity for CypD, and their binding mode within the enzyme's active site. Finally, approaches for improving the molecular design of CypD inhibitors are discussed.
On partially observed optimal singular control of McKean–Vlasov stochastic systems: Maximum principle approach
Authors: Abada Nour El Houda , Hafayed Mokhtar , Meherrem Shahlar
Published: May 2022

In this paper, we study partially observed optimal stochastic singular control problems of general Mckean–Vlasov type with correlated noises between the system and the observation. The control variable has two components, the first being absolutely continuous and the second is a bounded variation, nondecreasing continuous on the right with left limits. The dynamic system is governed by Itô‐type controlled stochastic differential equation. The coefficients of the dynamic depend on the state process and of its probability law and the continuous control variable. In terms of a classical convex variational techniques, we establish a set of necessary conditions of optimal singular control in the form of maximum principle. Our main result is proved by applying Girsanov's theorem and the derivatives with respect to probability law in Lions' sense. To illustrate our theoretical result, we study partially observed linear‐quadratic singular control problem of McKean–Vlasov type.
Accuracy investigations for volumetric head‐motion navigators with and without EPI at 7 T
Authors: Andersen Mads , Laustsen Malte , Boer Vincent
Published: May 2022

Purpose

Accuracy investigation of volumetric navigators for motion correction, with emphasis on geometric EPI distortions at ultrahigh field.

Methods

High‐resolution Dixon images were collected in different head positions and reconstructed to water, fat, T2*, and B0 maps. Resolution reduction was performed, and the T2* and B0 maps were used to apply effects of TE and EPI distortions to simulate various volumetric water and fat navigators. Registrations of the simulated navigators were compared with registrations of the original high‐resolution images.

Results

Increased accuracy was observed with increased spatial resolution for non‐EPI navigators. When using EPI, the distortions had a negative effect on registration accuracy, which was most noticeable for high‐resolution navigators. Parallel imaging helped to alleviate those caveats to a certain extent, and 5‐fold acceleration gave close to similar accuracy to non‐EPI in most cases. Shortening the TE by partial Fourier sampling was shown to be mostly beneficial, except for water navigators with long readout durations. The EPI blip direction had an influence on navigator accuracy, and positive blip gradient polarities (yielding mostly image stretching frontally) typically gave the best accuracy for water navigators, whereas no clear recommendation could be made for fat navigators. Generally, fat EPI navigators had lower accuracy than water EPI navigators with otherwise similar parameters.

Conclusions

Echo planar imaging has been widely used for MRI navigators, but the induced distortions reduce navigator accuracy at ultrahigh field. This study can help protocol optimization and guide the complex tradeoff between resolution and EPI acceleration in navigator parameter setup.
Investigating the role of filler shape on the dynamic mechanical properties of glass‐filled epoxy composites
Authors: Karunakaran Kathiresan , Singh Sarthak S. , Kitey Rajesh
Published: May 2022

The influence of filler shape and volume fraction on the dynamic mechanical characteristics of rigid glass filler epoxy composites is investigated. Two variants of glass fillers, spherical particle and slender (milled) fibers, are doped into the epoxy matrix till 10% volume fraction. The composites are room temperature cured and tested to measure their viscoelastic properties. The dynamic mechanical analyses performed in the temperature range of 20–180°C at 10 Hz suggest that the milled fiber composites display consistently higher storage and loss moduli, whereas the higher loss factor peaks were noted for the spherical particle composites. The C‐factor, filler reinforcement efficiency of the composites and entanglement density, evaluated from the storage modulus values, indicate that the milled fibers composites are more effective in transferring the loads in both glassy and rubbery zones when compared against the spherical particle case. Also, the filler/matrix adhesion factor (A factor) and the interphase adhesion factor, calculated from the loss factor curves reveal stronger filler/matrix interactions in the case of milled fiber epoxy composites. Interestingly, the filler geometry or volume fraction has only marginal influence on the glass transition temperature of the composites.
Non‐invasive prenatal screening for fetal triploidy using single nucleotide polymorphism‐based testing: Differential diagnosis and clinical management in cases showing an extra haplotype
Authors: Kantor Valerie , Jelsema Russ , Xu Wenbo , DiNonno Wendy , Young Kathryn , Demko Zachary , Benn Peter
Published: May 2022

Objective

An extra haplotype is infrequently encountered in single nucleotide polymorphism(SNP)‐based non‐invasive prenatal testing (NIPT) and is usually attributed to an undetected twin or triploidy. We reviewed a large series to establish relative frequencies of these outcomes and identify alternative causes.

Methods

In 515,804 women receiving NIPT from September 2017 through March 2019, all results with an extra haplotype were reviewed. Known viable and vanished twin pregnancies were excluded. For positive cases, pregnancy outcome information was sought.

Results

Of 1005 results with an extra haplotype (1 in 513), pregnancy outcome was available for 773 cases: 11% were confirmed or suspected triploidy; 65% to vanished twin; 10% with pregnancy loss. Rare explanations included complete mole, chimera, undisclosed donor egg pregnancy, maternal organ transplant and one instance of maternal neoplasm. Among triploid cases that were detected and independently confirmed, 23/27 (85%) were diandric.

Conclusion

SNP‐based NIPT, with detection of an extra haplotype, is 11% predictive of triploidy. For results with an extra haplotype, ultrasound is recommended to establish viability, evaluate for twins (viable or vanished), and detect findings consistent with triploidy. Review of patient history, serum screening, and ultrasound will reduce the number of CVS or amniocenteses necessary to confirm a diagnosis of triploidy.
Indications and outcome of home high‐flow nasal therapy in children, a single‐center experience
Authors: Steindor Mathis , Wagner Carolin Ellen , Kavvalou Alexandra , Bock Claudia , Olivier Margarete , Stehling Florian
Published: May 2022

High‐flow nasal therapy (HFNT) is a safe and simple way to deliver humidified air and oxygen for respiratory support in infants and children. HFNT is well established in an inpatient setting, but home HFNT lacks evidence. In the current study, we studied characteristics and outcomes of pediatric patients with home HFNT. In a monocentric retrospective analysis of data for 10 years (April 2010–April 2020), patient characteristics from the time point of the first discharge from hospital with home HFNT‐treatment and the subsequent course were analyzed. Patients were divided into three HFNT indication groups: (1) bronchopulmonary dysplasia (BPD), (2) upper airway obstruction (UAO), and (3) other indications. Forty patients received home HFNT in the study period. Seventeen patients were treated for BPD, 15 for UAO, and 8 had other indications. Twenty‐two patients (55%) were successfully weaned from HFNT (12 [70.6%] BPD, 7 [46.7%] UAO, 3 [37.5%] other), while seven patients (17.5%) died during follow‐up (4 BPD, 2 UAO, 1 other). Twenty‐three patients (57.5%) required (intermittent) additional oxygen application (14 [82.4%] BPD, 6 [40%] UAO, 4 [50%] other). Weaning success and need for additional oxygen were significantly more probable in BPD patients compared to the UOA group. In conclusion, HFNT plays an increasing role in home treatment of respiratory insufficiency of various etiologies in childhood. It often represents a temporary intervention, especially for children with BPD but might also serve as long‐term treatment for children in whom other forms of ventilatory support are not feasible or desired.
Ultrasound‐guided placement of long peripheral cannula in children with cystic fibrosis
Authors: Giardina Massimiliano , Barillà David , Crimi Claudia , Arone Amelia , Benedetto Filippo , Lucanto Cristina , Natoli Rossella , Messina Roberto , David Antonio , Noto Alberto
Published: May 2022

Background

The natural history of cystic fibrosis (CF) lung disease is a chronic deterioration of lung function with intermittent episodes of pulmonary infectious exacerbations (PExs). Reliable venous access is a milestone of effective management of such exacerbations, managed both in hospital and outpatient chronic therapy. The aim of our study was to analyze the feasibility of ultrasound‐guided positioning of long peripheral catheters (LPC) as reliable midterm venous access in children affected by CF.

Methods

In this single‐center prospective study, over a 60‐month period, we included paediatric CF subjects admitted with PExs and undergoing intravenous antibiotic treatment. LPCs were inserted in all participants by paediatric anaesthesiologists with ultrasound guide technique. Prospective data were collected assessing catheter positioning procedure and complications.

Results

A total of 122 LPC insertions were performed in 55 CF children. Participants had a median age of 6.75 years (interquatile range: 3.7−13.5) at the time of catheter insertion. Implantation was successful on the first attempt in 86% of cases; 2 (1%) major insertion‐related complications were reported. Eighty‐eight percent of catheters were electively removed at the end of antibiotic therapy without any complication. Seven percent of the catheters were removed electively for occlusion and 2% for local dislodgment.

Conclusions

The results of the present study suggest that ultrasound‐guided positioning of LPCs are safe alternative means of peripheral venous access in children with chronic diseases such as CF.
Effects of nicotinic acetylcholine receptor subunit deletion mutants on insecticide susceptibility and fitness in Drosophila melanogaster
Authors: Zhang Yan‐Chao , Pei Xin‐Guo , Yu Zhi‐Tao , Gao Yang , Wang Li‐Xiang , Zhang Ning , Song Xin‐Yu , Wu Shun‐Fan , Gao Cong‐Fen
Published: May 2022

BACKGROUND

Nicotinic acetylcholine receptors (nAChRs) are major excitatory neurotransmitter receptors in insects and also the target site for many insecticides. Unfortunately, the effectiveness of these insecticides is diminishing as a consequence of the evolution of insecticide resistance. Further exploration of insecticide targets is important to sustainable pest management.

RESULTS

In order to validate the role of nAChR subunits in insecticide susceptibility and test whether the subunit's absence imposes the fitness cost on insects, we determined the susceptibility of eight nAChR subunit deletion mutants of Drosophila melanogaster to nine insecticides. These findings highlighted the specific resistance of the Dα6 deletion mutant to spinosyns. Although triflumezopyrim, dinotefuran and imidacloprid are competitive modulators of nAChRs, differences in susceptibility of the insect with different deletion mutants suggested that the target sites of these three insecticides do not overlap completely. Mutants showed decreased susceptibility to insecticides, accompanied by a reduction in fitness. The number of eggs produced by Dα1attP, Dα2attP, Dβ2attP and Dβ3attP females was significantly lesser than that of the vas‐Cas9 strain as the control. In addition, adults of Dα2attP, Dα3attP and Dα7attP strains showed lower climbing performance. Meanwhile, males of Dα3attP, Dα5attP, Dβ2attP and Dβ3attP, and females of Dβ2attP showed significantly shorter longevity than those of the vas‐Cas9 strain.

CONCLUSION

This study provides new insights into the interactions of different insecticides with different nAChRs subunit in D. melanogaster as a research model, it could help better understand such interaction in agricultural pests whose genetic manipulations for toxicological research are often challenging. © 2022 Society of Chemical Industry.
Robust physiologically based pharmacokinetic model of rifampicin for predicting drug–drug interactions via P‐glycoprotein induction and inhibition in the intestine, liver, and kidney
Authors: Asaumi Ryuta , Nunoya Ken‐ichi , Yamaura Yoshiyuki , Taskar Kunal S. , Sugiyama Yuichi
Published: May 2022

P‐glycoprotein (P‐gp) is an efflux transporter that plays an important role in the pharmacokinetics of its substrate, and P‐gp activities can be altered by induction and inhibition effects of rifampicin. This study aimed to establish a physiologically based pharmacokinetic (PBPK) model of rifampicin to predict the P‐gp‐mediated drug–drug interactions (DDIs) and assess the DDI impact in the intestine, liver, and kidney. The induction and inhibition parameters of rifampicin for P‐gp were estimated using two of seven DDI cases of rifampicin and digoxin and incorporated into our previously constructed PBPK model of rifampicin. The constructed rifampicin model was verified using the remaining five DDI cases with digoxin and five DDI cases with other P‐gp substrates (talinolol and quinidine). Based on the established PBPK model, following repeated dosing of 600 mg rifampicin, the deduced net effect was an approximately threefold induction in P‐gp activities in the intestine, liver, and kidney. Furthermore, in all 12 cases the predicted area under the plasma concentration–time curve ratios of the P‐gp substrates were within the predefined acceptance criteria with various dosing regimens. Intestinal effects of P‐gp–mediated DDIs had their greatest impact on the pharmacokinetics of digoxin and talinolol, with a minimal impact on the liver and kidney. For quinidine, predicted intestinal P‐gp/cytochrome P450 3A–mediated DDIs were slightly underestimated because of the complexity of nonlinearity and transporter‐enzyme interplay. These findings demonstrate that our rifampicin model can be applicable to quantitatively predict the net impact of P‐gp induction and/or inhibition on diverse P‐gp substrates and investigate the magnitude of DDIs in each tissue.
The effect of curcumin supplementation on delayed‐onset muscle soreness, inflammation, muscle strength, and joint flexibility: A systematic review and dose–response meta‐analysis of randomized controlled trials
Authors: Beba Mohammad , Mohammadi Hamed , Clark Cain C. T. , Djafarian Kurosh
Published: May 2022

To quantify the effects of curcumin supplementation on exercise‐induced muscle damage, muscle soreness, inflammatory biomarkers, muscle strength, and joint flexibility via assessment of creatine kinase (CK), visual analogue scale (VAS) score, maximal voluntary contraction (MVC), and range of motion (ROM), respectively. Online databases, including PubMed, Google Scholar, and Scopus, were searched up to February 2021. RevMan® software (version 5.3) was used for assessing the risk of bias to assess the quality of studies. The mean differences (MD) and confidence intervals (95% CI) of CK activity (IU/L), VAS score, tumor necrosis factor (TNF‐α) (pg/ml), interleukin‐6 (IL‐6) (pg/ml), IL‐8 (pg/ml), MVC (nm) and ROM (degree) were pooled using a random‐ or fixed‐effect model. Between‐study heterogeneity was assessed using χ‐square or I2 statistic. Ten trials met the eligibility criteria and were included in the pooled analysis. Meta‐analysis showed that curcumin supplementation significantly reduced serum CK activity [WMD = −65.98 IU/L, 95% CI (−99.53 to −32.44)], muscle soreness [WMD = −0.56, 95% CI (−0.84 to −0.27)], and TNF‐α concentration [WMD = −0.22 pg/ml, 95% CI (−0.33 to −0.10)]. Also, curcumin supplementation elicited significant improvements in MVC [WMD = 3.10 nm, 95% CI (1.45–4.75)] and ROM [WMD = 6.49°, 95% CI (3.91–9.07)], although no significant changes in IL‐6 and IL‐8 levels were found. Dose–response analysis indicated that there is a significant non‐linear association between the daily dose and the final effect size regarding TNF‐α. Curcumin supplementation may improve some aspects of DOMS, including muscle damage, muscle soreness, inflammation, muscle strength, and joint flexibility. Further, well‐designed and high‐quality studies with larger sample sizes are needed to ascertain the long‐term effects and safety of curcumin supplementation.
Distributions and convergence of forecast variables in a 1,000‐member convection‐permitting ensemble
Authors: Craig George C. , Puh Matjaž , Keil Christian , Tempest Kirsten , Necker Tobias , Ruiz Juan , Weissmann Martin , Miyoshi Takemasa
Published: May 2022

The errors in numerical weather forecasts resulting from limited ensemble size are explored using 1,000‐member forecasts of convective weather over Germany at 3‐km resolution. A large number of forecast variables at different lead times were examined, and their distributions could be classified into three categories: quasi‐normal (e.g., tropospheric temperature), highly skewed (e.g. precipitation), and mixtures (e.g., humidity). Dependence on ensemble size was examined in comparison to the asymptotic convergence law that the sampling error decreases proportional to N−1/2 for large enough ensemble size N, independent of the underlying distribution shape. The asymptotic convergence behavior was observed for the ensemble mean of all forecast variables, even for ensemble sizes less than 10. For the ensemble standard deviation, sizes of up to 100 were required for the convergence law to apply. In contrast, there was no clear sign of convergence for the 95th percentile even with 1,000 members. Methods such as neighborhood statistics or prediction of area‐averaged quantities were found to improve accuracy, but only for variables with random small‐scale variability, such as convective precipitation.
Medical abortion via telemedicine for women and adolescents: Experience from Moldova
Authors: Comendant Rodica , Cook Clayborne , Hodorogea Stelian , Sagaidac Irina , Bubulici Cristina , Platais Ingrida
Published: May 2022

Introduction

To pilot and evaluate the safety and participant satisfaction of the first‐ever telemedicine medical abortion service provided in Moldova, a lower‐income country located in Eastern Europe.

Methods

Before enrolment, each participant confirmed their pregnancy with a urine pregnancy test, ultrasound and/or blood test and calculated the gestational age based on the last menstrual period. After study consent was obtained, the study clinician confirmed eligibility for medical abortion and the study and provided counselling via videoconference or telephone. Eligible participants received medications by mail or prescription. A follow‐up call to assess abortion outcome, adverse events and other medical history was conducted 1 week after participants took mifepristone. A pregnancy test was taken 4 weeks after taking mifepristone for a final evaluation of the abortion outcome. The analysis was descriptive.

Results

Between March 2020 and March 2021, 549 eligibility screenings were conducted, and 531 study packages containing medications or prescriptions were sent to pregnant women and adolescents with gestations ≤9 weeks since the last menstrual period. The majority of procedures (n = 477, 89.8%) were completed without an in‐person visit. Final abortion outcome was available for 499/531 (94.0%) medical abortion procedures: 484/499 (97.0%) were complete abortions, 11 (2.2%) were surgical completions (seven incomplete abortions and four continuing pregnancies), and four participants (0.8%) decided to keep their pregnancy. One serious adverse event occurred. Acceptability of the service was high (99.0% very satisfied or satisfied) and 86.5% of participants reported a future preference for telemedicine. The most commonly reported reasons for choosing the telemedicine service were convenience (n = 286, 56.2%) and confidentiality (n = 202, 39.7%).

Conclusion

The medical abortion via telemedicine service has proven to be a safe and acceptable option for women and adolescents in Moldova. This model has the potential to increase access to abortion, including during emergencies like the COVID‐19 pandemic.
Nutrient and sediment dynamics change following a major flood event on a large, grassland river
Authors: Chen Matthew , Guenther Mirae , Corman Jessica R.
Published: May 2022

River ecosystems can impact the quantity of materials and nutrients flowing into receiving waters. However, these processes may change with climate change, particularly with respect to the impacts of extreme flooding events. In this study, we examined the long‐term impacts of an extreme flooding event, the 2019 U.S. Midwest floods, on nutrient loads and concentrations in an unconfined, fourth‐order grassland stream, the Niobrara River, Nebraska. To compare historical trends to modern conditions, archived data and contemporarily sampled data were used in conjunction. Prior to the flood (1990–2018), NO3‐N concentrations showed a strong seasonal pattern with no relationship with discharge, indicating a groundwater NO3‐N source. Total phosphorus (TP), dissolved inorganic phosphorus (DIP), and total suspended solids (TSS) showed slight and individual seasonal patterns relating to discharge, following expected patterns of sediment sourced P. Post‐flood, NO3‐N concentrations declined by 91.5% (F[2, 269] = 34.96, p < .0001). NO3‐N depression in the system remained even once discharge returned to pre‐flood levels. TP, DIP, and TSS (F (2, 236) = 38.14, ANOVA p < .0001; F(2, 176) = 44.06, ANOVA p < .0001; F(2, 205) = 25.98, ANOVA p < .0001) each saw elevation of 100%, 117%, and 66% respectively in 2019 with an expected drop in 2020 when discharge returned to pre‐flood. It is unclear why NO3‐N concentrations, unlike phosphorus, did not return to pre‐flood levels in the 2 years of this study. The observation suggests extreme flooding events may cause complex, unexpected shifts in biogeochemical cycling in river ecosystems.
Dynamic prediction with time‐dependent marker in survival analysis using supervised functional principal component analysis
Authors: Shi Haolun , Jiang Shu , Cao Jiguo
Published: May 2022

Time‐varying biomarkers reflect important information on disease progression over time. Dynamic prediction for event occurrence on a real‐time basis, utilizing time‐varying information, is crucial in making accurate clinical decisions. Functional principal component analysis (FPCA) has been widely adopted in the literature for extracting features from time‐varying biomarker trajectories. However, feature extraction via FPCA is conducted independent of the time‐to‐event response, which may not produce optimal results when the goal lies in prediction. With this consideration, we propose a novel supervised FPCA, where the functional principal components are determined to optimize the association between the time‐varying biomarker and time‐to‐event outcome. The proposed framework also accommodates irregularly spaced and sparse longitudinal data. Our method is empirically shown to retain better discrimination and calibration performance than the unsupervised FPCA method in simulation studies. Application of the proposed method is also illustrated in the Alzheimer's Disease Neuroimaging Initiative database.
Security in IoMT‐driven smart healthcare: A comprehensive review and open challenges
Authors: Garg Neha , Wazid Mohammad , Singh Jaskaran , Singh D. P. , Das Ashok Kumar
Published: May 2022

The Internet of Medical Things (IoMT) is a kind of communication environment, which deals with communication that occurs through the Internet of Things (IoT)‐enabled smart medical (healthcare) devices. The potential security threats of IoMT affect the confidentiality, integrity, authenticity and availability of its data and the associated resources. In this review article, we explain various architectures of IoMT communication along with their applications. We highlight the security requirements of IoMT communication environment along with some potential security attacks and threats of IoMT. Furthermore, the network model and adversary model of IoMT communication are provided. A taxonomy of security protocols of IoMT communication environment is additionally added, which contains various security protocols, such as key management, user/device authentication, access control and intrusion detection protocols. Moreover, we provide a detailed comprehensive comparative analysis of several security protocols with respect to various parameters, like computation cost, communication cost, security features and functionality features, accuracy and F1‐score. Additionally, we also provide some future research directions.
Implementation of real‐time hybrid simulation based on GPU computing
Authors: Zhenyun Tang , Xiaohui Dong , Zhenbao Li , Xiuli Du
Published: May 2022

With combination of physical experiment and numerical simulation, real‐time hybrid simulation (RTHS) can enlarge the dimensions of testing specimens and improve the testing accuracy. However, due to the limitation of computing capacity, the maximum degrees of freedom for numerical substructure are less than 7000 from the reported RTHS testing. It cannot meet the testing requirements for evaluating the dynamic performance of large and complex engineering structures. Taking advantages of parallel computing toolbox (PCT) in Matlab and high‐performance computing of graphics processing unit (GPU). A RTHS framework based on MATLAB and GPU was established in this work. Using this framework, a soil‐structure interaction system (SSI) was tested by a shaking table based RTHS. Meanwhile, the dynamic response of this SSI system was simulated by finite element analysis. The comparison of simulation and testing results demonstrated that the proposed testing framework can implement RTHS testing successfully. Using this method, the maximum degrees of freedom for numerical substructure can reach to 27,000, which significantly enhance the testing capacity of RTHS testing for large and complex engineering structures.
Ambidexterity's influence on export strategy development—The case of the Indian pharmaceutical industry
Authors: Kolte Ashutosh , Festa Giuseppe , Rossi Matteo , Thrassou Alkis , Vrontis Demetris , Christofi Michael
Published: May 2022

This study investigates the influence that business ambidexterity of the Indian pharmaceutical industry can exert on exports, after the evolution from producer—often with the support of foreign direct investments (FDIs)—to researcher. The growth rate of the sector has changed pace with the introduction of new rules regarding patents, impelling pharma enterprises to invest in research and development (R&D), also for the peculiar category of AYUSH. However, many aspects of this industrial evolution are, if anything, under researched. To fill this gap in knowledge, this research adopts a quantitative methodology on secondary data to investigate the effects and potentialities of ambidexterity, providing evidence from descriptive and inferential statistics. Insisting on traditional production of generics (exploitation) and investing in R&D (exploration) have been coherent with the rise in exports, but several factors still impede the development of the commercial potential of the Indian pharmaceutical industry, mostly due to low per capita health care spending, absence of reliable infrastructure, and severe market competition.
Conflict and conflict resolution
Authors: Kirby Roger
Published: May 2022

In this editorial, Professor Roger Kirby, Editor‐in‐Chief of Trends in Urology and Men's Health, reflects on the increase of conflict in healthcare settings.
Use of bone anchors for the treatment of partial and complete traumatic elbow luxations: A retrospective case series of three dogs
Authors: Logothetou Vasileia , Pappa Eirini , Pettitt Rob , Comerford Eithne
Published: May 2022

Three dogs presented with traumatic lateral elbow luxation following road traffic accidents. Concurrent injuries included skin abrasions and coxofemoral luxation. All luxations were reduced and stabilised with bone anchors through a lateral approach to the elbow joint and had an augmented or prosthetic lateral collateral ligament placed. One elbow joint was stabilised with FASTak anchor (Arthrex, Karsfeld, Germany) and two with suture anchors by IMEX bone anchor (Veterinary, Longview, TX). Reluxation occurred in one case 24 hours after discharge requiring revision surgery. Median follow‐up time for the three cases was 180 days (range: 49–2920) and the functional outcome was considered excellent in all cases as determined by veterinary assessment, clinical record reviews, owner communication and Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. In conclusion, placement of bone anchors with augmentation of the lateral collateral ligament for management of traumatic elbow luxation in dogs is a good alternative to previously reported surgical techniques.
Free‐Standing Few‐Layer Tellurene Nanosheets: Simple Solution‐Phase Synthesis and Electronic Structure
Authors: Bhui Animesh , Roychowdhury Subhajit , Sen Arpita , Waghmare Umesh V. , Biswas Kanishka
Published: May 2022

Mechanical stirring of bulk Te in N‐methyl‐2‐pyrrolidone (NMP) solution at room temperature resulted in the formation of free‐standing few‐layer (∼1.2–2.8 nm) crystalline ultrathin nanosheets of tellurene with a large lateral thickness (∼1–1.6 μm) as confirmed by atomic force microscopy (AFM). High‐resolution transmission electron microscopy (HRTEM) confirms the presence of α‐ and β‐phases of tellurene. First‐principle density functional theoretical (DFT) based electronic structure calculations demonstrate the indirect band gap of bi‐layer β‐tellurene. The band gap decreases with increasing number of layers in the tellurene nanosheet.