bluuebunny/crossref_metadata_2025 huggingface dataset:
IL‐17 serum level in patients with chronic mucocutaneous candidiasis disease
Authors: Chimenz Roberto , Tropeano Angelo , Chirico Valeria , Ceravolo Giorgia , Salpietro Carmelo , Cuppari Caterina
Published: January 2022

Background

Chronic mucocutaneous candidiasis (CMC) is defined by recurrent or persistent superficial infections involving nails, skin, and/or oral and genital mucosae. IL‐17 promotes the recruitment, chemotaxis, and expansion of neutrophils and acts directly on keratinocytes and epithelial cells, driving the production of antimicrobial peptides, essential for the immune response against Candida.

Aim

To evaluate the serum level of IL‐17 in a family affected by CMC restricted to the nails of the hands and feet.

Methods

Serum IL‐17 was assayed on 16 patients (aged 21 ± 3.1 years) suffering from persistent onychomycosis caused by Candida and 18 healthy controls (aged 19 ± 2.7 years). Comparisons between groups were performed by Student's unpaired t‐test. The level of significance was set at 0.05.

Results

The mean serum IL‐17 level in patients was 74 ± 1.42 pg/ml, whereas the control group showed a significantly lower level of 25.6 ± 6.7 pg/ml (p < 0.05).

Conclusions

We showed a potential defect in the IL‐17 signaling pathway in a family affected by CMC restricted to the nails of the hands and feet. Further research is needed to clarify the immunological mechanisms and the genetic etiology at the basis of the unusual clinical presentation in this family.
Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta‐analysis
Authors: Signorino Claudia , Votto Martina , De Filippo Maria , Marseglia Gian Luigi , Galli Luisa , Chiappini Elena
Published: January 2022

Diagnosis of childhood tuberculosis (TB) is challenging. Xpert MTB/RIF and the new version Xpert MTB/RIF Ultra (Ultra) are molecular tests currently used to rapidly identify the infection. We reviewed the literature for the accuracy of Ultra assay in the diagnosis of tuberculosis and rifampicin resistance in children. We conducted a full search in PubMed, Web of Science (WOS), Embase, and Scopus, up to April 2021. A bivariate random‐effects model was used to determine the pooled sensitivity and specificity of Ultra, with a 95% confidence interval (CI), compared with culturing and the composite reference standard (CRS). In the ten included studies (2,427 participants), the pooled Ultra sensitivity and specificity, in diagnosing pulmonary tuberculosis (PTB), were 78% (95% CI, 73–82) and 92% (95% CI, 91–94), respectively, against culture. Since a high heterogeneity was found between studies, we created subgroups based on different samples and ages. Ultra‐pooled sensitivity was consistently lower against CRS (95% CI, 35%, 32–38). Compared to Xpert MTB/RIF, Ultra sensitivity tended toward higher values (Ultra: 73%, 67%–78% vs. Xpert MTB/RIF: 66%, 60%–72%), but specificity was lower (Ultra: 95%, 94%–96% vs. Xpert MTB/RIF: 99%, 98%–99%). Ultra has improved the definitive diagnosis of PTB, particularly in subjects with paucibacillary TB, including children. The lower specificity could be due to the fact that culture is an imperfect reference standard. Further studies are needed to evaluate the accuracy of Ultra in the diagnosis of childhood TB.
Novel artful applications of vaccines at the horizon
Authors: Montin Davide , Ottaviano Giorgio , Sangerardi Maria , Sgrulletti Mayla , Chini Loredana , Dellepiane Rosa Maria , Martire Baldassarre , Rizzo Caterina , Moschese Viviana
Published: January 2022

Some live vaccines, particularly Bacillus Calmette‐Guérin (BCG), oral polio vaccine (OPV), and measles vaccine, can reduce the incidence of all‐cause mortality by outreaching the mere control of specific infections and exerting off‐target effects. Asides from the prevention of viral infection, some other vaccines, such as those against flu or rotavirus, could reduce the risk of developing autoimmunity. The nonspecific effects of vaccines are mediated by the innate immune system, mainly through the so‐called trained innate immunity. These observations paved the way for developing tolerogenic and trained immunity‐based vaccines with substantial implications for more effective use of vaccines and combat vaccine hesitancy.
FDI and spillovers: New evidence from Malaysia’s manufacturing sector
Authors: Zhang Miao , Yang Rui
Published: January 2022

The spillover effects of foreign direct investment (FDI) are often viewed as potential contributors to economic growth and development in developing countries. As a developing country that adopts a proactive stance towards FDI, Malaysia provides a good setting to investigate whether and to what extent FDI‐induced spillovers potentially benefit national firms. Using an unpublished establishment‐level dataset comprising 10,953 manufacturing firms in 2015, this study examined the productivity and spillover effects of foreign manufacturing firms on national firms in Malaysia. While foreign firms exhibited higher productivity than national firms, the results showed that FDI generates high spillovers on national firms among FDI‐concentrated industries, but not on industries with low FDI concentrations. In response to methodological call by Melitz’s new‐new trade theory to include firms’ heterogeneity to understand the economy at macro‐ level, this study contends that the presence and extent of FDI‐induced spillover benefits on national firms depends on industry and firm characteristics. Thus, policy instruments must consider sector‐ and firm‐ specific characteristics to appropriate FDI spillovers as an enabler for national firms to survive, learn, catch up, and eventually compete in the global market.
Accelerometer derived physical activity patterns in 27.890 middle‐aged adults: The SCAPIS cohort study
Authors: Ekblom‐Bak Elin , Börjesson Mats , Bergman Frida , Bergström Göran , Dahlin‐Almevall Albin , Drake Isabel , Engström Gunnar , Engvall Jan E , Gummesson Anders , Hagström Emil , Hjelmgren Ola , Jernberg Tomas , Johansson Peter J , Lind Lars , Mannila Maria , Nyberg André , Persson Margaretha , Reitan Christian , Rosengren Annika , Rådholm Karin , Schmidt Caroline , Sköld Magnus C , Sonestedt Emily , Sundström Johan , Swahn Eva , Öhlin Jerry , Östgren Carl Johan , Ekblom Örjan
Published: January 2022

The present study aims to describe accelerometer‐assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle‐aged men and women, and to study differences between subgroups of socio‐demographic, socio‐economic, and lifestyle‐related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle‐aged men and women with at least four days of valid hip‐worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X‐BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All‐year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty‐eight percent was defined as having an “at‐risk” behavior, which included both high sedentary time and low vigorous PA. In this large population‐based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
Using very short answer errors to guide teaching
Authors: Putt Oliver , Westacott Rachel , Sam Amir H. , Gurnell Mark , Brown Celia A.
Published: January 2022

Background

Student performance in examinations reflects on both teaching and student learning. Very short answer questions require students to provide a self‐generated response to a question of between one and five words, which removes the cueing effects of single best answer format examinations while still enabling efficient machine marking. The aim of this study was to pilot a method of analysing student errors in an applied knowledge test consisting of very short answer questions, which would enable identification of common areas that could potentially guide future teaching.

Methods

We analysed the incorrect answers given by 1417 students from 20 UK medical schools in a formative very short answer question assessment delivered online.

Findings

The analysis identified four predominant types of error: inability to identify the most important abnormal value, over or unnecessary investigation, lack of specificity of radiology requesting and over‐reliance on trigger words.

Conclusions

We provide evidence that an additional benefit to the very short answer question format examination is that analysis of errors is possible. Further assessment is required to determine if altering teaching based on the error analysis can lead to improvements in student performance.
The mitochondrial LYR protein SDHAF1 is required for succinate dehydrogenase activity in Arabidopsis
Authors: Li Ying , Belt Katharina , Alqahtani Saad F. , Saha Saurabh , Fenske Ricarda , Van Aken Olivier , Whelan James , Millar A. Harvey , Murcha Monika W. , Huang Shaobai
Published: January 2022

Succinate dehydrogenase (SDH, complex II), which plays an essential role in mitochondrial respiration and tricarboxylic acid metabolism, requires the assembly of eight nuclear‐encoded subunits and the insertion of various cofactors. Here, we report on the characterization of an Arabidopsis thaliana leucine‐tyrosine‐arginine (LYR) protein family member SDHAF1, (At2g39725) is a factor required for SDH activity. SDHAF1 is located in mitochondria and can fully complement the yeast SDHAF1 deletion strain. Knockdown of SDHAF1 using RNA interference resulted in a decrease in seedling hypocotyl elongation and reduced SDH activity. Proteomic analyses revealed a decreased abundance of various SDH subunits and assembly factors. Protein interaction assays revealed that SDHAF1 can interact exclusively with the Fe‐S cluster‐containing subunit SDH2 and HSCB, a cochaperone involved in Fe‐S cluster complex recruitment. Therefore, we propose that in Arabidopsis, SDHAF1 plays a role in the biogenesis of SDH2 to form the functional complex II, which is essential for mitochondrial respiration and metabolism.
Are capital inflow bonanzas a common precursor to banking crises? A categorical data analysis
Authors: Roy Saktinil , Kemme David M.
Published: January 2022

The empirical literature that relates capital inflow bonanzas to the risk of a banking crisis has, so far, examined the probability of a crisis conditional on a bonanza episode. We argue that estimating the probability of a prior capital inflow bonanza, given the occurrence of a banking crisis, is at least equally important from a policy perspective to limit the exposure to sudden, big surges in capital inflows and reduce the risk of a systemic banking crisis. We consider two global samples, one consisting of 64 countries for 1970–2008 and the other 111 countries for 1980–2008. In both samples, we show that the latter conditional probability is strikingly large, much higher than the former, and even higher if we consider only "systemic" banking crises in developing countries. We also construct 2 × 2 contingency tables, utilise the odds ratio and conduct statistical tests to show that the association between bonanzas and crises is significant and robust across the two samples. The association is much stronger than commonly understood, most notably for systemic crises in developing countries. The findings provide support for stronger policies to limit or dampen unusual surges in international capital flows.
Shear wave elastography of lymph nodes in dogs with head and neck cancer: A pilot study
Authors: Favril Sophie , Stock Emmelie , Broeckx Bart J. G. , Devriendt Nausikaa , de Rooster Hilde , Vanderperren Katrien
Published: January 2022

Shear wave elastography (SWE) is a novel ultrasound imaging technique, used in human medicine to differentiate metastatic from non‐metastatic lymph nodes (LNs) based on higher tissue stiffness. The objective of this pilot study was to evaluate whether canine metastatic LNs were stiffer compared to non‐metastatic LNs. SWE of sentinel or regional LNs in dogs with head and neck cancer was performed. Ten elastograms of each LN were acquired. In each elastogram, mean, median, and maximum shear wave velocities (SWVs) were calculated in the most elastic region, the stiffest region, and the entire LN. The means of those SWVs for each region of each LN were subsequently calculated. Furthermore, a stepwise subsampling was performed to assess the effect of the number of acquired elastograms on the consistency of the classification of a LN as metastatic or not. Twenty‐four LNs in 15 dogs with head and neck cancer were included, of which 10 LNs were metastatic. Metastatic medial retropharyngeal and mandibular LNs were successfully distinguished from non‐metastatic LNs based on higher mean and median SWVs in the stiffest region and higher maximum SWVs in entire LNs. Furthermore, maximum SWVs in the stiffest region of mandibular LNs were higher in metastatic LNs compared to non‐metastatic LNs. Downstream analyses demonstrated that at least eight elastograms were necessary to perform reliable analyses. This pilot trial demonstrated that SWE has potential to discriminate metastatic from non‐metastatic LNs; however, LN status should be based on at least eight elastograms in future clinical trials.
Efficacy of a quaternary ammonium compound in reducing coagulase‐positive staphylococcal colony counts in veterinary dermatology exam rooms following two cleaning instruction protocols
Authors: Bennie Callum J. M. , Daniels Joshua B. , Rao Sangeeta , Rosychuk Rod A. W. , Schissler Jennifer R.
Published: January 2022

Background

Nosocomial meticillin‐resistant (MR) staphylococcal infections are of global concern. Veterinary dermatology exam room surfaces may be a reservoir given the commonness of staphylococcal pyoderma.

Hypothesis/Objectives

First, efficacy of exam room surface decontamination using a quaternary ammonium compound was assessed after use of two different cleaning instruction protocols. Second, coagulase‐positive staphylococcal (CoPS) colony counts were assessed after use of rooms by dogs with pyoderma, and then after cleaning and disinfection.

Methods and materials

In Part I, 10 room surfaces were tagged with a discreet fluorescent dye, Glo Germ, to assess the efficacy of surface cleaning between two Virex II 256‐based cleaning protocols. In Part II, CoPS colonies were quantified via 3M Staph Express System. Ten standardised room surfaces were sampled after use by a dog with staphylococcal pyoderma, and immediately after a detailed cleaning and disinfection protocol.

Results

A total of 24 of 100 and 81 of 100 surfaces were completely cleaned by the general and detailed protocols, respectively. The mean number of surfaces adequately cleaned was higher with the detailed protocol (P = 0.003). The detailed protocol reduced CoPS colony counts of eight surfaces (P < 0.01), and not chairs (P = 0.055). No CoPS were isolated from the exam table under a table mat.

Conclusions and clinical relevance

Detailed exam room cleaning and disinfection protocols are recommended to minimise contamination of veterinary exam room surfaces with staphylococci. The appropriate disinfection of chairs necessitates further study.
Retrospective evaluation of systemic hypertension in dogs with nonassociative (primary) immune‐mediated hemolytic anemia (December 2016 to April 2019): 26 cases
Authors: Hall Georgina B. F. , Stoye David Q. , Thomas Emily K. , Culshaw Geoff J.
Published: January 2022

Objective

To report the prevalence of arterial hypertension in a population of dogs with nonassociative immune‐mediated hemolytic anemia (IMHA) on presentation and during hospitalization. To determine the relationships of systolic blood pressure (SBP) with mortality and a prognostic indicator, the canine hemolytic anemia objective score.

Design

Retrospective observational study (December 2016 to April 2019).

Setting

University teaching hospital.

Animals

Twenty‐six clinical dogs presenting to the ICU with nonassociative (primary) IMHA and a control group of 23 clinical dogs with idiopathic epilepsy hospitalized in the ICU for seizure treatment or monitoring.

Interventions

None.

Measurements and Main Results

Hypertension was defined as SBP ≥ 160 mm Hg and severe hypertension as SBP ≥ 180 mm Hg. Mean SBP was significantly increased in IMHA dogs (161 mm Hg, SD = 21) compared to ICU control dogs (138 mm Hg, SD = 14; P < 0.005). Hypertension was present in 13 of 26 (50.0%) dogs across the period of hospitalization and was severe in three of 26 (11.5%). During at least 1 day of hospitalization, 18 of 26 (69.2%) dogs were hypertensive and eight of 26 (34.6%) were severely hypertensive. Hypertension was not associated with short‐term mortality or canine hemolytic anemia objective score.

Conclusions

In this retrospective study, hypertension was more prevalent in dogs with nonassociative IMHA than a control population of ICU‐hospitalized dogs. An association between autoimmune conditions and hypertension has been previously reported in people but not within a canine population. Hypertension in dogs may have an inflammatory or autoimmune etiology. SBP should be monitored closely in canine IMHA, in case antihypertensive treatment is required.
Impression Marketing as a Tool for Building Emotional Connections in the Public Administration Sphere
Authors: Likarchuk Nataliia , Andrieieva Olha , Likarchuk Daria , Bernatskyi Andrii
Published: January 2022

Marketing is an extremely dynamic and intensive phenomenon, and the transformations taking place in the modern market paradigm cause the emergence of impression marketing in different spheres including the political one. This article is aimed at the analysis of the marketing of impressions as a tool in the political sphere. Emotions that influence making decisions were identified. Ukrainian post-Maidan society was studied and the population reaction to President V. Zelensky’s emotional style of communication was analysed. As the result of the study, it was found that emotional marketing affects a person’s feelings, their emotional state and is associated with the creation of positive associations. It can be stated that modern politics is characterized by components of attraction, theatricality, entertainment. Action management in Ukrainian political space is studied and such examples as speeches by politicians, parliamentary sittings, arrests and searches of businessmen are provided. The general perception of the president was evaluated and it was found that the emotional feelings of the population are almost polar. It was concluded that emotions are an indicator of the political situation in the country and in Ukraine, in the political sphere, fear is one of the decisive emotions which, in particular, plays a mobilizing role. Thus, impression marketing is a powerful tool for adjusting the electorate to the emotional rhythm of information perception.
Torque- and Muscle-Driven Flexion Induce Disparate Risks of In Vitro Herniation: A Multiscale and Multiphasic Structure-Based Finite Element Study
Authors: Zhou Minhao , Huff Reece D. , Abubakr Yousuf , O'Connell Grace D.
Published: January 2022

The intervertebral disc is a complex structure that experiences multiaxial stresses regularly. Disc failure through herniation is a common cause of lower back pain, which causes reduced mobility and debilitating pain, resulting in heavy socioeconomic burdens. Unfortunately, herniation etiology is not well understood, partially due to challenges in replicating herniation in vitro. Previous studies suggest that flexion elevated risks of herniation. Thus, the objective of this study was to use a multiscale and multiphasic finite element model to evaluate the risk of failure under torque- or muscle-driven flexion. Models were developed to represent torque-driven flexion with the instantaneous center of rotation (ICR) located on the disc, and the more physiologically representative muscle-driven flexion with the ICR located anterior of the disc. Model predictions highlighted disparate disc mechanics regarding bulk deformation, stress-bearing mechanisms, and intradiscal stress–strain distributions. Specifically, failure was predicted to initiate at the bone-disc boundary under torque-driven flexion, which may explain why endplate junction failure, instead of herniation, has been the more common failure mode observed in vitro. By contrast, failure was predicted to initiate in the posterolateral annulus fibrosus under muscle-driven flexion, resulting in consistent herniation. Our findings also suggested that muscle-driven flexion combined with axial compression could be sufficient for provoking herniation in vitro and in silico. In conclusion, this study provided a computational framework for designing in vitro testing protocols that can advance the assessment of disc failure behavior and the performance of engineered disc implants.
Spectral Bandedness in High-Fidelity Computational Fluid Dynamics Predicts Rupture Status in Intracranial Aneurysms
Authors: MacDonald Daniel E. , Najafi Mehdi , Temor Lucas , Steinman David A.
Published: January 2022

Recent studies using high-fidelity computational fluid dynamics (CFD) have revealed high-frequency flow instabilities consistent with clinical reports of bruits and “musical murmurs”, which have been speculated to contribute to aneurysm growth and rupture. We hypothesized that harmonic flow instabilities (“spectral bandedness”) in aneurysm CFD data may be associated with rupture status. Before testing this hypothesis, we first present a novel method for quantifying and visualizing spectral bandedness in cardiovascular CFD datasets based on musical audio-processing tools. Motivated by previous studies of aneurysm hemodynamics, we also computed a selection of existing metrics that have demonstrated association with rupture in large studies. In a dataset of 50 bifurcation aneurysm geometries modeled using high-fidelity CFD, our spectral bandedness index (SBI) was the only metric significantly associated with rupture status (AUC = 0.76, p = 0.002), with a specificity of 79% (correctly predicting 19/24 unruptured cases) and sensitivity of 65% (correctly predicting 17/26 ruptured cases). Three-dimensional flow visualizations revealed coherent regions of high SBI to be associated with strong near-wall inflow jets and vortex-shedding/flutter phenomena in the aneurysm sac. We speculate that these intracycle, coherent flow instabilities may preferentially contribute to the progressive degradation of the aneurysm wall through flow-induced vibrational mechanisms, and that their absence in high-fidelity CFD may be useful for identifying intracranial aneurysms at lower risk of rupture.
Integral Form of the Heat Transfer Equation With Arbitrarily Moving Boundary and Arbitrary Heat Source
Authors: Novozhilov V. , Kulish V.
Published: January 2022

For the first time, an integral form of one-dimensional heat transfer equation in a semi-infinite domain with a boundary, moving arbitrarily in time, and a heat source, depending arbitrarily on time and space location, is obtained. The obtained integral equation relates time histories of the temperature and its gradient at the boundary of the domain with the temperature at any given point inside or at the boundary of the domain. In the latter case, it delivers closed form integral equation for the rate of boundary movement in nonlinear problems where the time history of boundary movement is one of problem unknowns. The obtained equation accounts explicitly for the presence of an arbitrary heat source in the domain, while other existing methods do not allow a closed integral formulation to be obtained in such a case. The equation may be used for an analytical investigation of several types of boundary value problems (BVPs), as well as for numerical solution of such problems. Particular cases of this equation with a trivial heat source are known to demonstrate chaotic behavior. It is expected that the same is true for some nontrivial heat source functions, and this conjecture will be explored in subsequent publications.
Generalized Bio-Heat Transfer Model Combining With the Relaxation Mechanism and Nonequilibrium Heat Transfer
Authors: Li Meijun , Wang Yingze , Liu Dong
Published: January 2022

The heat transport within living biological tissue is a complicated process coupled with various physiological activities. The nonhomogeneous inner anatomical structure leads to an essential difference from classical heat transfer. The generalized model of bioheat transfer involving the relaxation mechanism as well as nonequilibrium heat transfer is first proposed to explore the heat transport properties within living biological tissues. Due to the volume averaging theory, the new local instantaneous energy equations of blood and tissue are constructed separately by introducing the phase lags, in which the delay effect between the heat flux and temperature gradient absent in existing generalized models is considered. The effective phase lags covering the delay effect and nonequilibrium effect are obtained on this basis. A detailed parametric study has been conducted to estimate the values of these effective phase lags and evaluate their contributions on heat transport within living biological tissues. The results state that the effective phase lags depend on the anatomical structure of tissues and its physical properties. The delay effect is dominated in general and has a higher temperature elevation than that induced by nonequilibrium effect only.
Investigation of the Effect of the Stages Number, the Impeller Outlet Width, and the Impeller Outlet Angle on the Performance of an Industrial Electric Submersible Pump
Authors: Firatoglu Zeynel A. , Alihanoglu Mustafa N.
Published: January 2022

This study has investigated the effect of the number of stages, the blade outlet spacing, and the blade outlet angle of a selected industrial submersible pump on the pump performance. The main steps in the study are outlined below: Firstly, the operating characteristics in different stages of a selected industrial submersible pump were measured by the experiment. Following the measurements, the effects of two basic geometric parameters, such as impeller outlet width and impeller outlet angle on the pump performance were examined with computational fluid dynamics (CFD) simulations verified by the experimental measurements. It was seen that the geometric parameters, which were considered in the simulations, changed the size of the time-dependent variables, but the flow structure did not. Another striking finding from the CFD simulations carried out is it has been observed that while geometric arrangements have a partial effect on the flow structure along with the pump, they cause a difference in the critical values on the basic variables that define pump performance, such as pressure.
Numerical Simulation and Experimental Study on Hydraulic Bursting Failure of Aluminum Alloy T-Shaped Tube in Hydroforming
Authors: Fan Yubin , Xu Xuefeng , Wu Yiwang , Wei Liming , Huang Lin , Xiao Yao
Published: January 2022

In this work, the hydraulic bursting method was used to investigate the bursting failure of aluminum alloy as-formed T-shaped tube by hydroforming, which consisted of the rupture region and bursting pressure. The bursting pressure was calculated by theoretical formula and two finite element models of T-shaped tubes with uniform thickness and hydroforming thickness were established. The hydraulic bursting failure simulation and experiment was carried out. In the simulation results, the failure directions of T-shaped tubes with uniform thickness were along the circumferential direction, while the failure directions of T-shaped tubes with hydroforming thickness were along axis of the main tube. Through stress analysis, the allowable circumferential film stress was about 1/2 of the allowable axial film stress, which indicated that the rupture failure should be along axis of the main tube. The failure location appeared at the shoulder. The fractured morphology was observed by scanning electron microscopy (SEM). A large number of equiaxed dimples and secondary phase particles appeared in the failure location. The experimental results were consistent with the simulation results of the as-formed T-shaped tube by hydroforming. Finally, the accuracy of the bursting pressure formula was evaluated according to the experimental results.
Robust Vibration Control for Active Suspension System of In-Wheel-Motor-Driven Electric Vehicle Via μ-Synthesis Methodology
Authors: Jin Xianjian , Wang Jiadong , Yan Zeyuan , Xu Liwei , Yin Guodong , Chen Nan
Published: January 2022

This paper proposes a robust vibration controller design for active suspension system of in-wheel-motor-driven electric vehicles (IWMD-EVs) based on unified μ-synthesis framework. First, multiple parameter uncertainties and unmodeled high-order dynamics of the suspension are analyzed and discussed. By applying the mixed uncertainties and linear fraction transformation, model perturbations are separated from the suspension system and their perturbation bounds can also be limited. Then, the uncertain quarter-vehicle active suspension model with dynamic damping in-wheel-motor-driven system is established, in which in-wheel motor is suspended as a dynamic vibration absorber. The resulting robust μ-synthesis feedback controller of generalized closed-loop active suspension system is designed with the concept of structured singular value (SSV) μ and μ-synthesis theoretics, and solved via comprehensive solution of the D–G–K iteration. The μ analysis results show that the μ-controller possesses less conservative stability and performance margins as compared to the H∞ method against system uncertainties. Furthermore, simulations of nominal and perturbed suspension systems are implemented and the corresponding frequency and time-domain responses are compared, and then simulation results confirm that the developed μ-controller is capable of attenuating the negative vibration of the active suspension system compared with H∞ controller and passive suspension.
Review of Methods and Results for Reactor Physics Analysis of Thorium-Based Fuels From Irradiation Experiments Conducted in the National Research Universal Reactor
Authors: Sinh Nguyen T. , Wang Xiaolin , Bromley Blair P.
Published: January 2022

The development of advanced fuels and fuel cycles for conventional Generation III+ reactors, advanced reactors (such as Generation IV), and small modular reactors will help ensure the long-term sustainability and safety of the use of nuclear energy. Thorium-based fuels are an example of an advanced fuel that could augment and extend uranium resources. As part of previous efforts in Canada to investigate the use of thorium-based fuels for potential use in pressure-tube heavy-water reactors and other technologies, irradiation experiments with various thorium-containing fuels had been conducted in the National Research Universal (NRU) reactor at the Chalk River Laboratories. The NRU reactor physics computational tools and methods, developed initially for conventional enriched uranium fuel, had also been extended for analysis of thorium-based fuel experiments, with most satisfactory results. In this study, a number of physics and operation factors have been analyzed to quantify their effects on the production and burnup of 233U in thorium-based fuel, as well as to improve both the analysis and the use of thorium fuels and fuel cycles.
Effects of radial stress on piezoelectric ceramic tubes and transducers
Authors: Zhang X. F. , Lin X. J. , Yang C. H. , Cheng X. , Huang S. F.
Published: January 2022

Static analysis is performed for fiber windings to quantitatively control the radial stress at the outer radius of the piezoelectric ceramic tube. The radial stress is verified both experimentally and theoretically, and the dependence of the resonant and material properties of the piezoelectric ceramic tubes on the radial stress is clarified. The resonance frequencies and dielectric loss remain relatively stable, but the relative permittivity and the short circuit elastic constant decrease with the radial stress. The variations of the increased bandwidth and decreased electromechanical coupling coefficient (k31), piezoelectric constant (d31 and g31), and mechanical quality factor (Qm) are associated with the height-to-radius ratio. The properties of three cylindrical transducers applied with various radial stress show similar change tendencies, and a difference of 0.34 MPa radial stress results in a variation of approximately 13 in the bandwidth, 14 in Qm, 15 in k31, d31, and g31, and 16 in the amplitude of the first pulse. These results suggest that the consistency of the radial stress is essential, and it should be relatively small. These findings guide the design and preparation of the enhanced transducer.
Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter
Authors: Chaptal Vincent , Zampieri Veronica , Wiseman Benjamin , Orelle Cédric , Martin Juliette , Nguyen Kim-Anh , Gobet Alexia , Di Cesare Margot , Magnard Sandrine , Javed Waqas , Eid Jad , Kilburg Arnaud , Peuchmaur Marine , Marcoux Julien , Monticelli Luca , Hogbom Martin , Schoehn Guy , Jault Jean-Michel , Boumendjel Ahcène , Falson Pierre
Published: January 2022

Multidrug ABC transporters translocate drugs across membranes by a mechanism for which the molecular features of drug release are so far unknown. Here, we resolved three ATP-Mg
2+
–bound outward-facing conformations of the
Bacillus subtilis
(homodimeric) BmrA by x-ray crystallography and single-particle cryo–electron microscopy (EM) in detergent solution, one of them with rhodamine 6G (R6G), a substrate exported by BmrA when overexpressed in
B. subtilis
. Two R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1–2 of one monomer and TM5′–6′ of the other. They induce a rearrangement of TM1–2, highlighting a local flexibility that we confirmed by hydrogen/deuterium exchange and molecular dynamics simulations. In the absence of R6G, simulations show a fast postrelease occlusion of the cavity driven by hydrophobicity, while when present, R6G can move within the cavity, maintaining it open.
Monitoring and adapting cancer treatment using circulating tumor DNA kinetics: Current research, opportunities, and challenges
Authors: Sanz-Garcia Enrique , Zhao Eric , Bratman Scott V. , Siu Lillian L.
Published: January 2022

Circulating tumor DNA (ctDNA) has emerged as a biomarker with wide-ranging applications in cancer management. While its role in guiding precision medicine in certain tumors via noninvasive detection of susceptibility and resistance alterations is now well established, recent evidence has pointed to more generalizable use in treatment monitoring. Quantitative changes in ctDNA levels over time (i.e., ctDNA kinetics) have shown potential as an early indicator of therapeutic efficacy and could enable treatment adaptation. However, ctDNA kinetics are complex and heterogeneous, affected by tumor biology, host physiology, and treatment factors. This review outlines the current preclinical and clinical knowledge of ctDNA kinetics in cancer and how early on-treatment changes in ctDNA levels could be applied in clinical research to collect evidence to support implementation in daily practice.
Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy
Authors: Bonaventura Paola , Alcazer Vincent , Mutez Virginie , Tonon Laurie , Martin Juliette , Chuvin Nicolas , Michel Emilie , Boulos Rasha E. , Estornes Yann , Valladeau-Guilemond Jenny , Viari Alain , Wang Qing , Caux Christophe , Depil Stéphane
Published: January 2022

Human endogenous retroviruses (HERVs) represent 8% of the human genome. HERV products may represent tumor antigens relevant for cancer immunotherapy. We developed a bioinformatic approach to identify shared CD8
+
T cell epitopes derived from cancer-associated HERVs in solid tumors. Six candidates among the most commonly shared HLA-A2 epitopes with evidence of translation were selected for immunological evaluation. In vitro priming assays confirmed the immunogenicity of these epitopes, which induced high-avidity CD8
+
T cell clones. These T cells specifically recognize and kill HLA-A2
+
tumor cells presenting HERV epitopes on HLA molecules, as demonstrated by mass spectrometry. Furthermore, epitope-specific CD8
+
T cells were identified by dextramer staining among tumor-infiltrating lymphocytes from HLA-A2
+
patients with breast cancer. Last, we showed that HERV-specific T cells lyse patient-derived organoids. These shared virus-like epitopes are of major interest for the development of cancer vaccines or T cell–based immunotherapies, especially in tumors with low/intermediate mutational burden.
Unexplored Antarctic meteorite collection sites revealed through machine learning
Authors: Tollenaar Veronica , Zekollari Harry , Lhermitte Stef , Tax David M.J. , Debaille Vinciane , Goderis Steven , Claeys Philippe , Pattyn Frank
Published: January 2022

Meteorites provide a unique view into the origin and evolution of the Solar System. Antarctica is the most productive region for recovering meteorites, where these extraterrestrial rocks concentrate at meteorite stranding zones. To date, meteorite-bearing blue ice areas are mostly identified by serendipity and through costly reconnaissance missions. Here, we identify meteorite-rich areas by combining state-of-the-art datasets in a machine learning algorithm and provide continent-wide estimates of the probability to find meteorites at any given location. The resulting set of ca. 600 meteorite stranding zones, with an estimated accuracy of over 80%, reveals the existence of unexplored zones, some of which are located close to research stations. Our analyses suggest that less than 15% of all meteorites at the surface of the Antarctic ice sheet have been recovered to date. The data-driven approach will greatly facilitate the quest to collect the remaining meteorites in a coordinated and cost-effective manner.
Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq–guided combination with sapanisertib
Authors: Lim Chaemin , Dismuke Taylor , Malawsky Daniel , Ramsey Jacob D. , Hwang Duhyeong , Godfrey Virginia L. , Kabanov Alexander V. , Gershon Timothy R. , Sokolsky-Papkov Marina
Published: January 2022

The therapeutic potential of CDK4/6 inhibitors for brain tumors has been limited by recurrence. To address recurrence, we tested a nanoparticle formulation of CDK4/6 inhibitor palbociclib (POx-Palbo) in mice genetically-engineered to develop SHH-driven medulloblastoma, alone or in combination with specific agents suggested by our analysis. Nanoparticle encapsulation reduced palbociclib toxicity, enabled parenteral administration, improved CNS pharmacokinetics, and extended mouse survival, but recurrence persisted. scRNA-seq identified up-regulation of glutamate transporter
Slc1a2
and down-regulation of diverse ribosomal genes in proliferating medulloblastoma cells in POx-Palbo–treated mice, suggesting mTORC1 signaling suppression, subsequently confirmed by decreased 4EBP1 phosphorylation. Combining POx-Palbo with the mTORC1 inhibitor sapanisertib produced mutually enhancing effects and prolonged mouse survival compared to either agent alone, contrasting markedly with other tested drug combinations. Our data show the potential of nanoparticle formulation and scRNA-seq analysis of resistance to improve brain tumor treatment and identify POx-Palbo + Sapanisertib as effective combinatorial therapy for SHH medulloblastoma.
Bright, noniridescent structural coloration from clay mineral nanosheet suspensions
Authors: Michels-Brito Paulo H. , Dudko Volodymyr , Wagner Daniel , Markus Paul , Papastavrou Georg , Michels Leander , Breu Josef , Fossum Jon Otto
Published: January 2022

Structural colors originate by constructive interference following reflection and scattering of light from nanostructures with periodicity comparable to visible light wavelengths. Bright and noniridescent structural colorations are highly desirable. Here, we demonstrate that bright noniridescence structural coloration can be easily and rapidly achieved from suspended two-dimensional nanosheets of a clay mineral. We show that brightness is enormously improved by using double clay nanosheets, thus optimizing the clay refractive index that otherwise hampers structural coloration from such systems. Intralayer distances, and thus the structural colors, can be precisely and reproducibly controlled by clay concentration and ionic strength independently, and noniridescence is readily and effortlessly obtained in this system. Embedding such clay-designed nanosheets in recyclable solid matrices could provide tunable vivid coloration and mechanical strength and stability at the same time, thus opening a previously unknown venue for sustainable structural coloration.
A programmable and skin temperature–activated electromechanical synergistic dressing for effective wound healing
Authors: Yao Guang , Mo Xiaoyi , Yin Chenhui , Lou Wenhao , Wang Qian , Huang Sirong , Mao Linna , Chen Sihong , Zhao Kangning , Pan Taisong , Huang Lin , Lin Yuan
Published: January 2022

Mechanical regulation and electric stimulation hold great promise in skin tissue engineering for manipulating wound healing. However, the complexity of equipment operation and stimulation implementation remains an ongoing challenge in clinical applications. Here, we propose a programmable and skin temperature–activated electromechanical synergistic wound dressing composed of a shape memory alloy-based mechanical metamaterial for wound contraction and an antibacterial electret thin film for electric field generation. This strategy is successfully demonstrated on rats to achieve effective wound healing in as short as 4 and 8 days for linear and circular wounds, respectively, with a statistically significant over 50% improvement in wound closure rate versus the blank control group. The optimally designed electromechanical synergistic stimulation could regulate the wound microenvironment to accelerate healing metabolism, promote wound closure, and inhibit infection. This work provided an effective wound healing strategy in the context of a programmable temperature-responsive, battery-free electromechanical synergistic biomedical device.
Autonomous robotic laparoscopic surgery for intestinal anastomosis
Authors: Saeidi H. , Opfermann J. D. , Kam M. , Wei S. , Leonard S. , Hsieh M. H. , Kang J. U. , Krieger A.
Published: January 2022

Autonomous robotic surgery has the potential to provide efficacy, safety, and consistency independent of individual surgeon’s skill and experience. Autonomous anastomosis is a challenging soft-tissue surgery task because it requires intricate imaging, tissue tracking, and surgical planning techniques, as well as a precise execution via highly adaptable control strategies often in unstructured and deformable environments. In the laparoscopic setting, such surgeries are even more challenging because of the need for high maneuverability and repeatability under motion and vision constraints. Here we describe an enhanced autonomous strategy for laparoscopic soft tissue surgery and demonstrate robotic laparoscopic small bowel anastomosis in phantom and in vivo intestinal tissues. This enhanced autonomous strategy allows the operator to select among autonomously generated surgical plans and the robot executes a wide range of tasks independently. We then use our enhanced autonomous strategy to perform in vivo autonomous robotic laparoscopic surgery for intestinal anastomosis on porcine models over a 1-week survival period. We compared the anastomosis quality criteria—including needle placement corrections, suture spacing, suture bite size, completion time, lumen patency, and leak pressure—of the developed autonomous system, manual laparoscopic surgery, and robot-assisted surgery (RAS). Data from a phantom model indicate that our system outperforms expert surgeons’ manual technique and RAS technique in terms of consistency and accuracy. This was also replicated in the in vivo model. These results demonstrate that surgical robots exhibiting high levels of autonomy have the potential to improve consistency, patient outcomes, and access to a standard surgical technique.
Loss of miR-31-5p drives hematopoietic stem cell malignant transformation and restoration eliminates leukemia stem cells in mice
Authors: Zhu Biying , Zhong Wenbin , Cao Xiuye , Pan Guoping , Xu Mengyang , Zheng Jie , Chen Huanzhao , Feng Xiaoqin , Luo Chengwei , Lu Chen , Xiao Jie , Lin Weize , Lai Chaofeng , Li Mingchuan , Du Xin , Yi Qing , Yan Daoguang
Published: January 2022

Leukemia stem cells (LSCs) propagate leukemia and are responsible for the high frequency of relapse of treated patients. The ability to target LSCs remains elusive, indicating a need to understand the underlying mechanism of LSC formation. Here, we report that miR-31-5p is reduced or undetectable in human LSCs compared to hematopoietic stem progenitor cells (HSPCs). Inhibition of miR-31-5p in HSPCs promotes the expression of its target gene
FIH
, encoding FIH [factor inhibiting hypoxia-inducing factor 1α (HIF-1α)], to suppress HIF-1α signaling. Increased FIH resulted in a switch from glycolysis to oxidative phosphorylation (OXPHOS) as the predominant mode of energy metabolism and increased the abundance of the oncometabolite fumarate. Increased fumarate promoted the conversion of HSPCs to LSCs and initiated myeloid leukemia-like disease in NOD-Prkdc
scid
IL2rg
tm1
/Bcgen (B-NDG) mice. We further demonstrated that miR-31-5p inhibited long- and short-term hematopoietic stem cells with a high frequency of LSCs. In combination with the chemotherapeutic agent Ara-C (cytosine arabinoside), restoration of miR-31-5p using G7 poly (amidoamine) nanosized dendriplex encapsulating miR-31-5p eliminated LSCs and inhibited acute myeloid leukemia (AML) progression in patient-derived xenograft mouse models. These results demonstrated a mechanism of HSC malignant transformation through altered energy metabolism and provided a potential therapeutic strategy to treat patients with AML.
Distinct Metabolic Flow in Response to Temperature in Thermotolerant Kluyveromyces marxianus
Authors: Kosaka Tomoyuki , Tsuzuno Tatsuya , Nishida Seiki , Pattanakittivorakul Sornsiri , Murata Masayuki , Miyakawa Isamu , Lertwattanasakul Noppon , Limtong Savitree , Yamada Mamoru
Published: January 2022

Kluyveromyces marxianus
, a thermotolerant yeast, can grow well at temperatures over 45°C, unlike
Kluyveromyces lactis
, which belongs to the same genus, or
Saccharomyces cerevisiae
, which is a closely related yeast.
K. marxianus
may thus bear an intrinsic mechanism to survive at high temperatures. This study revealed the thermotolerant mechanism of the yeast, including ROS scavenging with NADPH, which is generated by changes in metabolic flow.
Interaction between Avian Leukosis Virus Subgroup J Surface Protein and Doublecortin-Like Kinase 1 Accelerates Cell Proliferation and Epithelial-Mesenchymal Transition
Authors: Zhou Jing , Zhou Defang , Du Xusheng , Xue Jingwen , Yang Jianhao , Wang Guihua , Cheng Ziqiang
Published: January 2022

Tumor metastasis is a major challenge in cancer research, because of its systemic nature and the resistance of disseminated tumor cells to existing therapeutic agents. It is estimated that >90% of mortality from cancer is attributable to metastases.