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Abstract Background Sociocultural competence is essential for health professions education (HPE) students. However, the relationships between university campus environment, sense of belonging, and sociocultural engagement of HPE students remain unclear. We hypothesized that a university environment promoting students’ participation in social activities enhances their sociocultural engagement, which is mediated through the students’ sense of belonging, ultimately increasing their satisfaction with university experience. Methods The study included undergraduate HPE students (n = 638) at Gulf Medical University. We used a validated questionnaire for measuring sociocultural engagement of students (13 items). In addition, we used scales for measuring the supportive campus environment (8 items), quality of student relationships (4 items), students’ sense of belonging (5 items), and student satisfaction with university experience (one item). We examined the relationships between the study variables using path analysis. Results The campus environment had direct significant effects on the two dimensions of sociocultural engagement: sociocultural interactions and sociocultural adaptation (β = 0.18 and 0.24, P

Abstract The development of GaN-based Micro-LED arrays achieving brightnesses exceeding 107 nits and high-density micro-displays with up to 1080×780 pixels marks a true breakthrough in the field. This breakthrough is a result of mastering a combination of long-standing challenges comprising wafer-scale high-quality epitaxial growth, sidewall passivation, efficient photon extraction, and elegant bonding technologies, and promises significant advantages for augmented and virtual reality devices, wearables, and next-generation consumer electronics.

Abstract The high redox potential of Zn0/2+ leads to low voltage of Zn batteries and therefore low energy density, plaguing deployment of Zn batteries in many energy-demanding applications. Though employing high-voltage cathode like spinel LiNi0.5Mn1.5O4 can increase the voltages of Zn batteries, Zn2+ ions will be immobilized in LiNi0.5Mn1.5O4 once intercalated, resulting in irreversibility. Here, we design a polymer hetero-electrolyte consisting of an anode layer with Zn2+ ions as charge carriers and a cathode layer that blocks the Zn2+ ion shuttle, which allows separated Zn and Li reversibility. As such, the Zn‖LNMO cell exhibits up to 2.4 V discharge voltage and 450 stable cycles with high reversible capacity, which are also attained in a scale-up pouch cell. The pouch cell shows a low self-discharge after resting for 28 days. The designed electrolyte paves the way to develop high-voltage Zn batteries based on reversible lithiated cathodes.

Abstract Background Sociocultural engagement of students refers to broadening viewpoints and providing awareness of, and respect for, diverse backgrounds and perspectives. However, there are no existing validated instruments in the literature for measuring sociocultural engagement of health professions education (HPE) students. Therefore, the aim of this study is to develop and validate a questionnaire designed to assess sociocultural engagement among HPE students. Methods The study included undergraduate HPE students (n = 683) at Gulf Medical University. The initial version of the sociocultural engagement of students’ questionnaire (SESQ) was developed after extensive literature review and guided by the Global Learning Qualifications Framework. We then tested the content validity of the questionnaire by using focus group discussion with subject experts (n = 16) and pilot testing with students (n = 20). We distributed the content-validated version of the SESQ (16 items) to undergraduate students in six HPE colleges. To examine the construct validity and construct reliability of the questionnaire, we conducted exploratory factor analysis, followed by confirmatory factor analysis. Results Confirmatory factor analysis supported the two-factor structure which consists of 13 items with good fitness indices (χ2 = 214.35, df = 61, χ 2/df = 3.51, CFI = 0.98, RMSEA = 0.06, SRMR = 0.025, and AIC = 208.00). The two factors were sociocultural interactions (8 items) and sociocultural adaptation (5 items). The construct reliability of the total questionnaire is 0.97 and the two factors were 0.93 and 0.92 for sociocultural interactions and sociocultural adaptation, respectively. In addition, there were significant weak correlations between both factors of sociocultural engagement scores and student satisfaction with the university experience (r = .19 for each, P = .01). Conclusions The sociocultural engagement of students’ questionnaire exhibits good evidence of construct validity and reliability. Further studies will be required to test the validity of this questionnaire in other contexts.

Study RegionKachemak Bay is a fjord-type estuary in the northern Gulf of Alaska. Water quality and habitat characteristics are strongly influenced by freshwater and sediment input from multiple glacierized catchments.Study FocusWe present a new method combining imaging spectroscopy from an airborne survey with Landsat and Sentinel-2 imagery to map water surface turbidity originating from glacial runoff based on spectral abundance. We compare the spectral characteristics of turbid glacial water to clear water and generate a high resolution reference map of glacial turbidity in Kachemak Bay. This informs the subsequent analysis of a homogenized, Rayleigh corrected time series of Landsat and Sentinel-2 images and seasonal patterns of turbidity.New Hydrological Insights for the RegionOur results provide the most comprehensive data set on water surface turbidity in Kachemak Bay to date and improve understanding of spatial and seasonal variability of glacial turbidity in a data sparse region. July and August have the largest plumes with median sizes around 150 km2, or around a quarter of Kachemak Bay. Plume sizes typically decrease with decreasing glacier runoff in September and October. We show that imaging spectroscopy aids assessments of turbid water in glacial marine catchments across scales. Leveraging high resolution spectral information allows for water color analyses that are customized to local conditions and catchment characteristics as well as scalable to wider regions.

Abstract Active sensing matrices play a pivotal role in various electronic devices, including optical and X‐ray imaging arrays, electronic skins, and artificial tactile arrays, among others. These matrices function through a thin‐film active switching mechanism, allowing for the scanning of rows and columns by external circuitry to read the sensory signals of individual pixels. Recently, indium–gallium‐zinc oxide thin‐film transistors (IGZO TFTs) have emerged as highly promising technology in the realm of flexible electronics. They enable the large‐scale integration of functional circuits on flexible substrates. Shift registers are commonly employed as peripheral scanning circuits to sequentially address active‐matrix arrays. To enhance system compactness and minimize external electrical connections, it is imperative to seamlessly integrate shift registers within the active matrices. However, contemporary flexible IGZO‐based shift registers suffer from high operating voltages and low frequencies, which constrain their applicability in high‐performance flexible sensors and displays. In response to this challenge, a breakthrough is presented in the form of low‐voltage, high‐frequency bootstrap shift registers implemented with flexible IGZO technology. The approach involves utilizing SU‐8 buffered polyimide (PI) polymer foils as substrates. These foils boast an exceptional level of surface smoothness, significantly increasing the yield and performance of electronic components, including vias, IGZO TFTs, and capacitors used in the shift register circuitry. Additionally, HfO2/Al2O3/HfO2 sandwich structures are employed as high‐k dielectric layers to reduce the operational voltage. Thanks to the innovative circuit design and optimized fabrication methods, the 16‐stage shift register can operate at just 1.8 V with a frequency of 15 kHz. This breakthrough promises to have a profound impact on a wide range of applications for driving flexible active‐matrix electronic systems.

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat’s innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover.

Abstract Modification of the magnetic properties under the induced strain and curvature is a promising avenue to build three-dimensional magnetic devices, based on the domain wall motion. So far, most of the studies with 3D magnetic structures were performed in the helixes and nanowires, mainly with stationary domain walls. In this study, we demonstrate the impact of 3D geometry, strain and curvature on the current-induced domain wall motion and spin-orbital torque efficiency in the heterostructure, realized via a self-assembly rolling technique on a polymeric platform. We introduce a complete 3D memory unit with write, read and store functionality, all based on the field-free domain wall motion. Additionally, we conducted a comparative analysis between 2D and 3D structures, particularly addressing the influence of heat during the electric current pulse sequences. Finally, we demonstrated a remarkable increase of 30% in spin-torque efficiency in 3D configuration.

Abstract Generation of second-harmonic waves is one of the universal nonlinear phenomena that have found numerous technical applications in many modern technologies, in particular, in photonics. This phenomenon also has great potential in the field of magnonics, which considers the use of spin waves in magnetic nanostructures to implement wave-based signal processing and computing. However, due to the strong frequency dependence of the phase velocity of spin waves, resonant phase-matched generation of second-harmonic spin waves has not yet been achieved in practice. Here, we show experimentally that such a process can be realized using a combination of different modes of nano-sized spin-wave waveguides based on low-damping magnetic insulators. We demonstrate that our approach enables efficient spatially-extended energy transfer between interacting waves, which can be controlled by the intensity of the initial wave and the static magnetic field.

Background and Aims: Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort. Methods: A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively. Results: Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure. Conclusions: In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed. Impact and implications: Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.

Summary: The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.

A common practice in digital soil mapping (DSM) is to incorporate many environmental covariates into a machine-learning algorithm to predict the spatial patterns of soil attributes. Variance inflation factor (VIF), principal component analysis (PCA), and recursive feature elimination (RFE) are three statistical methods that can be used to reduce the number of covariates. This study aims 1) to compare VIF and PCA approaches; 2) to identify an approach to determine the minimum number of covariates in DSM to ensure model parsimony using RFE after using VIF; and 3) to examine methods to interpret the impact of covariates on the variability of the predicted soil properties. The study area was the province of British Columbia (BC), Canada. This study used legacy data for four soil properties to make digital soil maps: soil organic carbon (SOC%), pH, clay%, and coarse fragment (CF%). Seven models were made for each soil property to determine the influence on validation results by using a different number of covariates produced by various methods on validation results. The results showed that the number of covariates could be reduced from 70 to 4 to 12 with only a little or no difference in concordance correlation coefficient (CCC) validation results. The CCC results of pH models using 70 and 7 covariates were both 0.74, and for other soil properties, this difference was negligible. The validation results obtained from PCA models showed that the performance of PCA in reducing the number of covariates was not as effective as when using VIF. Moreover, this study showed that covariates related to precipitation were the most important for modeling SOC%, soil pH, and clay%. Topographic covariates were the most influential covariates for modeling soil CF%. This study emphasizes the potential benefits of combining various data reduction methods to achieve optimal outcomes and generate the most parsimonious and interpretable models.

Abstract Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

Abstract Background Student engagement is student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. Although previous studies provided some evidence of measuring student engagement in PBL tutorials, there are no existing quantitative studies in which cognitive, behavioral, and emotional engagement of students in PBL tutorials is measured. Therefore, this study aims to develop and examine the construct validity of a questionnaire for measuring cognitive, behavioral, and emotional engagement of students in PBL tutorials. Methods A 15-item questionnaire was developed guided by a previously published conceptual framework of student engagement. Focus group discussion (n = 12) with medical education experts was then conducted and the questionnaire was piloted with medical students. The questionnaire was then distributed to year 2 and 3 medical students (n = 176) in problem-based tutorial groups at the end of an integrated course, where PBL is the main strategy of learning. The validity of the internal structure of the questionnaire was tested by confirmatory factor analysis using structural equation modeling assuming five different models. Predictive validity evidence of the questionnaire was studied by examining the correlations between students’ engagement and academic achievement. Results Confirmatory factor analysis indicates a good fit between the measurement and structural model of an 11-item questionnaire composed of a three-factor structure: behavioral engagement (3 items), emotional engagement (4 items), and cognitive engagement (4 items). Models in which the three latent factors were considered semi-independent provided the best fit. The construct reliabilities of behavioral, cognitive, and emotional factors were 0.82, 0.82, and 0.76, respectively. We failed however to find significant relationships between academic achievement and engagement. Conclusions We found a strong evidence to support the construct validity of a three-factor structure of student engagement in PBL tutorial questionnaire. Further studies are required to test the validity of this instrument in other educational settings. The predictive validity is another area needing further scrutiny.

Reversible metal electrodeposition (RME)-based electrochromic devices have been attracting significant research interest due to their merits of low cost, simple configuration, and high extinction coefficients. As the key component in the electrochromic system, RME electrolytes with various metal ions and additives have endowed the RME device with flexible functionalities in energy-saving applications such as energy-efficient displays, smart windows, and camouflages. However, it is still challenging to research a widespread commercial application before some critical issues can be solved such as poor reversibility, low optical memory of the mirror state, and slow switching speed. Here, we offer a critical review of the recent progress of RME electrochromic devices based on aqueous, organic, ionic liquid, and eutectic electrolytes. Furthermore, the main challenges and perspectives for RME electrolytes are highlighted and discussed.

Abstract Dytiscus latissimus (Coleoptera Dytiscidae) is an endangered diving beetle throughout its range. It is one of the two species of Dytiscidae listed in Annex II of the Habitats Directive, IUCN red list and in many national level legislations and therefore strictly protected. The conservation of endangered species first of all requires an assessment of their population size. Until now, a method has not been developed for estimating the size of D. latissimus populations. The article summarizes the results of two studies carried out independently in Germany and Latvia. Both studies were carried out in one water body used recapture method but with a different spatial placement of traps, which, according to our data, is an important factor in population estimation. We evaluated Jolly-Seber and Schnabel approaches of estimating aquatic beetle's populations and found that confidence intervals obtained by different methods in our research do not differ significantly, but combination of both models provide the most accurate estimates of population dynamics. As part of the study, we concluded that the populations of Dytiscus latissimus are relatively closed, so we accept that the Schnabel estimate shows more accurate data. By fixing the places of capture of each individual, it was found that females live mainly locally, and males actively move within the water body. This aspect indicates the advantage of the spatial placement of traps compared to the use of transects. The results of our study show a significantly higher number of both captured and recaptured males Such a sex ratio may indicate both a greater activity of males and differences in the sex ratio in the population. The study confirmed that environmental changes, such as the water level in a water body, can also significantly affect the result of a population assessment. In the frame of D. latissimus monitoring, to obtain an objective estimation of the species population size we recommend using four traps for each 100 m of water body shoreline with 4–8 censuses, dependently on the recapture rate.

The neurotransmitter:sodium symporters (NSSs) are secondary active transporters that couple the reuptake of substrate to the symport of one or two sodium ions. One bound Na+ (Na1) contributes to the substrate binding, while the other Na+ (Na2) is thought to be involved in the conformational transition of the NSS. Two NSS members, the serotonin transporter (SERT) and the Drosophila dopamine transporter (dDAT), also couple substrate uptake to the antiport of K+ by a largely undefined mechanism. We have previously shown that the bacterial NSS homologue, LeuT, also binds K+, and could therefore serve as a model protein for the exploration of K+ binding in NSS proteins. Here, we characterize the impact of K+ on substrate affinity and transport as well as on LeuT conformational equilibrium states. Both radioligand binding assays and transition metal ion FRET (tmFRET) yielded similar K+ affinities for LeuT. K+ binding was specific and saturable. LeuT reconstituted into proteoliposomes showed that intra-vesicular K+ dose-dependently increased the transport velocity of [3H]alanine, whereas extra-vesicular K+ had no apparent effect. K+ binding induced a LeuT conformation distinct from the Na+- and substrate-bound conformation. Conservative mutations of the Na1 site residues affected the binding of Na+ and K+ to different degrees. The Na1 site mutation N27Q caused a >10-fold decrease in K+ affinity but at the same time a ~3-fold increase in Na+ affinity. Together, the results suggest that K+ binding to LeuT modulates substrate transport and that the K+ affinity and selectivity for LeuT is sensitive to mutations in the Na1 site, pointing toward the Na1 site as a candidate site for facilitating the interaction with K+ in some NSSs.

The investigation of topological state transition in carefully designed photonic lattices is of high interest for fundamental research, as well as for applied studies such as manipulating light flow in on‐chip photonic systems. Herein, the topological phase transition between symmetric topological zero modes (TZM) and antisymmetric TZMs in Su–Schrieffer–Heeger mirror symmetric waveguides is reported. The transition of TZMs is realized by adjusting the coupling ratio between neighboring waveguide pairs, which is enabled by selective modulation of the refractive index in the waveguide gaps. Bidirectional topological transitions between symmetric and antisymmetric TZMs can be achieved with proposed switching strategy. Selective excitation of topological edge mode is demonstrated owing to the symmetry characteristics of the TZMs. The flexible manipulation of topological states is promising for on‐chip light flow control and may spark further investigations on symmetric/antisymmetric TZM transitions in other photonic topological frameworks.

The development of direct-acting antivirals to combat COVID-19 remains an important goal. Here the authors design covalent inhibitors that target the papain-like protease from SARS-CoV-2. The most promising inhibitor blocks viral replication in mammalian cells.

Abstract Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.

Abstract Background Medical trainees often encounter situations that trigger emotional reactions which may hinder learning. Evidence of this effect on medical trainees is scarce and whether it could be counteracted is unclear. This study investigated the effect of negative emotions on medical residents’ learning and whether cognitive reappraisal counteracts it. Methods Ninety-nine medical residents participated in a three-phase experiment consisting of: (1) watching a video, either a neutral or an emotion-induction version, the latter either followed by cognitive reappraisal or not (2) learning: all participants studied the same medical text; study-time and cognitive engagement were measured; (3) test: a recall-test measured learning. Data was analysed using Chi-square test and one-way ANOVA. Results Study time significantly varied between conditions (p = 0.002). The two emotional conditions spent similar time, both significantly less than the neutral condition. The difference in test scores failed to reach significance level (p = 0.053). While the emotional conditions performed similarly, their scores tended to be lower than those of the neutral condition. Conclusion Negative emotions can adversely affect medical residents’ learning. The effect of emotions was not counteracted by cognitive reappraisal, which has been successfully employed to regulate emotions in other domains. Further research to examine emotion regulation strategies appropriate for medical education is much needed.

BackgroundPrescription opioid misuse risk is disproportionate among veterans; military veterans wounded in combat misuse prescription opioids at an even higher rate (46.2%). Opioid misuse is costly in terms of morbidity, mortality, and humanitarian and economic burden and costs the Civilian Health and Medical Program of the Department of Veterans Affairs more than US $1.13 billion annually. Preventing opioid misuse at the time of prescription is a critical component in the response to the opioid crisis. The CPMRx mobile app has been shown to decrease the odds of opioid misuse during the postoperative period. ObjectiveThe overarching purpose of this feasibility pilot study was to explore whether deploying a mobile app (CPMRx) to track postoperative pain and medication use is feasible in a Department of Veterans Affairs medical center. In support of this goal, we had four complementary specific aims: (1) determine the technological and logistical feasibility of the mobile app, (2) assess the acceptability of the mobile app to participants, (3) measure demand for and engagement with the mobile app, and (4) explore the potential use of the mobile app to patients and providers. MethodsParticipants (N=10) were veterans undergoing total knee arthroplasty within the Veterans Health Administration provided with the CPMRx app to self-manage their pain during their 7-day at-home recovery following surgery. CPMRx uses scientifically validated tools to help clinicians understand how a patient can use the least amount of medication while getting the most benefit. The suite of software includes a mobile app for patients that includes a behavioral health intervention and a clinical decision support tool for health care providers that provides feedback about pain and medication use trends. Patients filled out paper questionnaires regarding acceptability at their postoperative follow-up appointment. ResultsOverall, quantitative measures of acceptability were high. The average rating for the amount of time required to use the app was 4.9 of 5 (5=“very little”), and the average rating for ease of use was 4.4 of 5 (5=“very easy”). Open-ended questions also revealed that most participants found ease of use to be high. Demand and engagement were high as well with a mean number of mobile app entries of 34.1 (SD 20.1) during the postoperative period. There were no reported technological or logistical issues with the mobile app. Participants took an average of 25.13 (SD 14.37) opioid tablets to manage their postoperative pain. ConclusionsResults of this study revealed that the use of a mobile app for pain and medication management during postoperative recovery was both feasible and acceptable in older veterans undergoing total knee arthroplasty within the Veterans Health Administration. The wide variation in opioid consumption across participants revealed the potential use of the mobile app to provide actionable insights to clinicians if adopted more widely.

Ceramic foam filters are applied to remove non-metallic inclusions during steel melt filtration. The flame-spray technology can contribute to improving such filters by increasing the deposition capability of inclusions and decreasing the impairment of the filter substrate by the steel melt. This makes them suitable for application to the continuous steel casting process and foundry casting. The ball-on-three-balls test was utilized at elevated temperatures to determine the high-temperature behaviour of thermally sprayed alumina. Additionally, the flame-spray technology was used to produce carbon-free filters composed of flame-sprayed alumina by coating and burning out the Al2O3–C filter substrate during a sintering step. The B3B revealed a ductile behaviour with increasing temperature and a bending strength of 23.28 MPa at 1400 °C. After sintering at 1400 °C, the filters showed a sufficient CCS of 0.16 MPa, which allows the performance of casting tests (immersion and pouring) with molten steel at 1580 °C.

Abstract The extension of 2D ferromagnetic structures into 3D curved geometry enables to tune its magnetic properties such as uniaxial magnetic anisotropy. Tuning the anisotropy with strain and curvature has become a promising ingredient in modern electronics, such as flexible and stretchable magnetoelectronic devices, impedance-based field sensors, and strain gauges, however, has been limited to extended thin films and to only moderate bending. By applying a self-assembly rolling technique using a polymeric platform, we provide a template that allows homogeneous and controlled bending of a functional layer adhered to it, irrespective of its shape and size. This is an intriguing possibility to tailor the sign and magnitude of the surface strain of integrated, micron-sized devices. In this article, the impact of strain and curvature on the magnetic ground state and anisotropy is quantified for thin-film Permalloy micro-scale structures, fabricated on the surface of the tubular architectures, using solely electrical measurements.

Ketamine is shown to enhance excitatory synaptic drive in multiple brain areas, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamine’s therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that reduces excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment in cultured mouse hippocampal neurons significantly reduces Ca2+ and calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately leads to the expression of Ca2+-Permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). The ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and glutamate receptor plasticity in cultured hippocampal neurons. Moreover, when a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within 1 hr after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamine’s effects on animals’ behaviors. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity, which in turn enhances synaptic strength to induce rapid antidepressant actions.

Abstract MXenes add dozens of metallic conductors to the family of two‐dimensional (2D) materials. A top‐down synthesis approach removing A‐layer atoms (e.g., Al, Si, and Ga) in MAX phases to produce 2D flakes attaches various surface terminations to MXenes. With these terminations, MXenes show tunable properties, promising a range of applications from energy storage devices to electronics, including sensors, transistors, and antennas. MXenes are also excellent building blocks to create flexible films used for flexible and wearable devices. This article summarizes the synthesis of MXene flakes and highlights aspects that need attention for flexible devices. Rather than listing the development of energy storage devices in detail, we focus on the main challenges of and solutions for constructing high‐performance devices. Moreover, we show the applications of MXene films in electronics to call on designs to construct a complete system based on MXene with good flexibility, which consists of a power source, sensors, transistors, and wireless communications.

Abstract Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (Mpro also known as 3CLpro) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the Mpro Cys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the Mpro as potential COVID-19 therapeutics for further testing and possibly clinical trials.

Electron beam manipulation is important for their application in microscopes, lithography instruments, and colliders. Here the authors report a wafer scale, self-assembled, microcoil electrically-driven magnetic charge particle optic device that can be implemented into different configurations for controlling of electron beams.

The dopamine transporter, DAT, controls dopamine signaling by facilitating its reuptake using the Na+ gradient as driving force. Here, the authors uncover that an antiport of K+ ions also contributes to setting the rate of DAT-mediated dopamine clearance.

Developing molecular electronics is challenged by integrating fragile organic molecules into modern micro/nanoelectronics based on inorganic semiconductors. Li et al. apply rolled-up nanotechnology to assemble on-chip molecular devices, which can be switched between photodiodes and volatile memristors.

State-of-the-art magnetic skins can only sense in one or two-dimensions, at small spatial resolutions. By combining the ancient art of paper folding, origami, with advanced semiconductor technology, here, authors present cutting edge three-dimensional magnetic sensors.

Abstract Background Diagnostic error is a major source of patient suffering. Researchshows that physicians experience frequent interruptions while being engaged with patients and indicate that diagnostic accuracy may be impaired as a result. Since most studies in the field are observational, there is as yet no evidence suggesting a direct causal link between being interrupted and diagnostic error. Theexperiments reported in this article were intended to assess this hypothesis. Methods Three experiments were conducted to test the hypothesis that interruptions hurt diagnostic reasoning and increase time on task. In the first experiment (N = 42), internal medicine residents, while diagnosing vignettes of actual clinical cases were interrupted halfway with a task unrelated to medicine, solving word-spotting puzzles and anagrams. In the second experiment (N = 78), the interruptions were medically relevant ones. In the third experiment (N = 30), we put additional time pressure on the participants. In all these experiments, a control group diagnosed the cases without interruption. Dependent variables were diagnostic accuracy and amount of time spent on the vignettes. Results In none of the experiments interruptions were demonstrated to influence diagnostic accuracy. In Experiment 1: Mean of interrupted group was 0.88 (SD = 0.37) versus non- interrupted group 0.91 (SD = 0.32). In Experiment 2: Mean of interrupted group was 0.95 (SD = 0.32) versus non-interrupted group 0.94 (SD = 0.38). In Experiment 3: Mean of interrupted group was 0.42 (SD = 0.12) versus non-interrupted group 0.37 (SD = 0.08). Although interrupted residents in all experiments needed more time to complete the diagnostic task, only in Experiment 2, this effect was statistically significant. Conclusions These three experiments, taken together, failed to demonstrate negative effects of interruptions on diagnostic reasoning. Perhaps physicians who are interrupted may still have sufficient cognitive resources available to recover from it most of the time.

Summary: Immunogens that elicit broadly neutralizing antibodies targeting the conserved receptor-binding site (RBS) on influenza hemagglutinin may serve as candidates for a universal influenza vaccine. Here, we develop a computational model to interrogate antibody evolution by affinity maturation after immunization with two types of immunogens: a heterotrimeric “chimera” hemagglutinin that is enriched for the RBS epitope relative to other B cell epitopes and a cocktail composed of three non-epitope-enriched homotrimers of the monomers that comprise the chimera. Experiments in mice find that the chimera outperforms the cocktail for eliciting RBS-directed antibodies. We show that this result follows from an interplay between how B cells engage these antigens and interact with diverse helper T cells and requires T cell-mediated selection of germinal center B cells to be a stringent constraint. Our results shed light on antibody evolution and highlight how immunogen design and T cells modulate vaccination outcomes.

Across the surface of Mars, evidence of past lacustrine and evaporitic environments has been found within basins and craters, where often layered sedimentary deposits and hydrated minerals are observed. However, the intensity, duration, and precise phases of aqueous processes during their deposition remain unresolved mostly for our inability to model subsurface structures. Although several geological processes and locations on Earth have been previously proposed as examples to describe these deposits on Mars, we lack a strong visualization of what water activity might have looked like during evaporitic stages within basins and craters. Here we propose to investigate the shallow subsurface of the Makgadikgadi salt pans of Botswana as a potential analog for understanding groundwater upwelling on Mars. The pans are found within the Makgadikgadi Basin, a depression located at the southwestern end of a northeast-southwest set of graben linked with the East African Rift. The Makgadikgadi Pans are evaporitic environment rich in hydrated minerals and groundwater activity. The purpose of this work is to identify buried faults and areas of relative water saturation within the lacustrine sediment of the Makgadikgadi Basin by means of electrical resistivity surveys. This work represents the first electrical resistivity survey of the basin floor which provides a precursory investigation of the relationship between groundwater, faults, basement depth, and the lacustrine sediments. We present four electrical survey lines from different locations in the pans which reveal distinct sedimentary units. Several faults are inferred from the vertical displacement of these units and accompanying low resistivity where displacement is observed. These results provide a framework for visualizing the sedimentary sequences of infilled basins and craters on Mars, which can broaden the ongoing discussion of hydrogeological processes that were active in the planet’s past. We propose Meridiani Planum, as well as Oyama and Becquerel crater of Arabia Terra as locations to establish this framework. Since such processes are still ongoing in the Makgadikgadi Basin, imaging the subsurface of the pans helps explain the formation of layered and salty deposits on the surface of Mars, how they may have interacted with flowing water, and whether they might have hosted life.

Abstract Antibody immunodominance refers to the preferential and asymmetric elicitation of antibodies against specific epitopes on a complex protein antigen. Traditional vaccination approaches for rapidly evolving pathogens have had limited success in part because of this phenomenon, as elicited antibodies preferentially target highly variable regions of antigens, and thus do not confer long lasting protection. While antibodies targeting functionally conserved epitopes have the potential to be broadly protective, they often make up a minority of the overall repertoire. Here, we discuss recent protein engineering strategies used to favorably alter patterns of immunodominance, and selectively focus antibody responses toward broadly protective epitopes in the pursuit of next-generation vaccines for rapidly evolving pathogens.

Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antigen requires a specific set of mutations – distributed across the variable light and heavy chains – that interact non-additively (i.e., epistatically). These sets of mutations form a hierarchical pattern across the antigens, with increasingly divergent antigens requiring additional epistatic mutations beyond those required to bind less divergent antigens. We investigate the underlying biochemical and structural basis for these hierarchical sets of epistatic mutations and find that epistasis between heavy chain mutations and a mutation in the light chain at the VH-VL interface is essential for binding a divergent H1. Collectively, this is the first work to comprehensively characterize epistasis between heavy and light chain mutations and shows that such interactions are both strong and widespread. Together with our previous study analyzing a different class of anti-influenza antibodies, our results implicate epistasis as a general feature of antibody sequence-affinity landscapes that can potentiate and constrain the evolution of breadth.

Abstract Background COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C–C chemokine receptor type 5 (CCR5). Patient and methods An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients’ humoral antiviral immune response patterns by longitudinal observation. Results Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. Conclusion The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

Abstract Background The coronavirus disease 2019 (COVID‐19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain‐like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear. Patients and methods 6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database. Results Eleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals. Conclusion Our data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

The miniaturization of biocompatible microsystems that enable self-sufficiency and autarkic operations is ever increasing. Here, the authors demonstrate a robust integratable nano-biosupercapacitor with enhanced performance in complex biological fluids, thus enabling autarkic sensor operation in blood.

A variety of modern applications including soft robotics, prosthetics, and health monitoring devices that cover electronic skins (e‐skins), wearables as well as implants have been developed within the last two decades to bridge the gap between artificial and biological systems. During this development, high‐density integration of various sensing modalities into flexible electronic devices becomes vitally important to improve the perception and interaction of the human bodies and robotic appliances with external environment. As a key component in flexible electronics, the flexible thin‐film transistors (TFTs) have seen significant advances, allowing for building flexible active matrices. The flexible active matrices have been integrated with distributed arrays of sensing elements, enabling the detection of signals over a large area. The integration of sensors within pixels of flexible active matrices has brought the application scenarios to a higher level of sophistication with many advanced functionalities. Herein, recent progress in the active matrix flexible sensory systems is reviewed. The materials used to construct the semiconductor channels, the dielectric layers, and the flexible substrates for the active matrices are summarized. The pixel designs and fabrication strategies for the active matrix flexible sensory systems are briefly discussed. The applications of the flexible sensory systems are exemplified by reviewing pressure sensors, temperature sensors, photodetectors, magnetic sensors, and biosignal sensors. At the end, the recent development is summarized and the vision on the further advances of flexible active matrix sensory systems is provided.

Since the emergence of SARS-CoV-2 (SARS-2), multiple vaccine candidates were developed and studied both preclinically and clinically. Nearly all are based on the SARS-2 spike glycoprotein or its receptor binding domain (RBD). Studies of these vaccine candidates have largely been in a SARS-2 naïve context. However, pre-existing immunity to SARS-2 acquired through infection or vaccination continues to increase. Evaluating future vaccine candidates in context of this pre-existing immunity is necessary to understand how immune responses are subsequently influenced. Here, we evaluated the serum and IgG+ B cell responses to the SARS-2 RBD in context of pre-existing immunity elicited by the full SARS-2 spike, and we compared this to boosting with the full SARS-2 spike. Boosting with the SARS-2 RBD resulted in increased reactivity to RBD epitopes, but both immunization regimens resulted in similarly broad neutralization across diverse sarbecoviruses. These findings may inform comparison among SARS-2 RBD-based vaccine candidates to currently approved spike-based candidates.

Rechargeable microbatteries are important power supplies for microelectronic devices. Two essential targets for rechargeable microbatteries are high output energy and minimal footprint areas. In addition to the development of new high-performance electrode materials, the device configurations of microbatteries also play an important role in enhancing the output energy and miniaturizing the footprint area. To make a clear vision on the design principle of rechargeable microbatteries, we firstly summarize the typical configurations of microbatteries. The advantages of different configurations are thoroughly discussed from the aspects of fabrication technologies and material engineering. Towards the high energy output at a minimal footprint area, a revolutionary design for microbatteries is of great importance. In this perspective, we review the progress of fabricating microbatteries based on the rolled-up nanotechnology, a derivative origami technology. Finally, we discussed the challenges and perspectives in the device design and materials optimization.

The rapid development of wearable and portable electronics has dramatically increased the application for miniaturized energy storage components. Stamping micro-supercapacitors (MSCs) with planar interdigital configurations are considered as a promising candidate to meet the requirements. In this review, recent progress of the different stamping materials and various stamping technologies are first discussed. The merits of each material, manufacturing process of each stamping method and the properties of stamping MSCs are scrutinized, respectively. Further insights on technical difficulties and scientific challenges are finally demonstrated, including the limited thickness of printed electrodes, poor overlay accuracy and printing resolution.

Skin mountable electronic devices are in a high-speed development at the crossroads of materials science, electronics, and computer science. Sophisticated functions, such as sensing, actuating, and computing, are integrated into a soft electronic device that can be firmly mounted to any place of human body. These advanced electronic devices are capable of yielding abilities for us whenever they are needed and even expanding our abilities beyond their natural limitations. Despite the great promise of skin mounted electronic devices, they still lack satisfactory power supplies that are safe and continuous. This Perspective discusses the prospects of the development of energy storage devices for the next generation skin mountable electronic devices based on their unique requirements on flexibility and miniaturized size.

Abstract Background Diagnostic errors have been attributed to cognitive biases (reasoning shortcuts), which are thought to result from fast reasoning. Suggested solutions include slowing down the reasoning process. However, slower reasoning is not necessarily more accurate than faster reasoning. In this study, we studied the relationship between time to diagnose and diagnostic accuracy. Methods We conducted a multi-center within-subjects experiment where we prospectively induced availability bias (using Mamede et al.’s methodology) in 117 internal medicine residents. Subsequently, residents diagnosed cases that resembled those bias cases but had another correct diagnosis. We determined whether residents were correct, incorrect due to bias (i.e. they provided the diagnosis induced by availability bias) or due to other causes (i.e. they provided another incorrect diagnosis) and compared time to diagnose. Results We did not successfully induce bias: no significant effect of availability bias was found. Therefore, we compared correct diagnoses to all incorrect diagnoses. Residents reached correct diagnoses faster than incorrect diagnoses (115 s vs. 129 s, p