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We derive a coupled-mode theory (CMT) formulation for the fast analysis of periodic multi-element metasurfaces in the presence of radiation losses. Full-wave simulations of periodic multi-element metasurfaces are very time- and memory-consuming, especially as the size and complexity of the metasurface increase. The CMT formulation provides a considerably faster and efficient alternative. It results in a small system of equations with size equal to the number of supported resonator modes in the frequency range of interest, allowing to calculate the resonator mode amplitudes and, consequently, the metasurface response. Subsequently, we systematically derive analytical closed-form expressions for the coupling coefficients between two weakly coupled resonators in the presence of radiation losses and incorporate them into the CMT model, which is found important for the accurate description of the metasurface, while also providing insight into the underlying physics of complex metasurfaces. We validate the proposed formulation on benchmark examples of both metal- and dielectric-based metasurface absorbers (MSAs) by comparing the CMT results to spectral FEM simulations of the composing supercell. To further demonstrate the potential of the proposed formulation, as a proof of concept, we use the CMT to synthesize a larger optimized periodic multi-element MSA. A comprehensive comparison to full-wave FEM simulations of the composing supercell is included in terms of time and computational requirements, which shows that our method provides a valuable and efficient alternative solver for synthesizing complex metasurfaces. [ABSTRACT FROM AUTHOR]

Cavity coupling of gas-phase molecules will enable studies of benchmark chemical processes under strong light–matter interactions with a high level of experimental control and no solvent effects. We recently demonstrated the formation of gas-phase molecular polaritons by strongly coupling bright ν3, J = 3 → 4 rovibrational transitions of methane (CH4) to a Fabry–Pérot optical cavity mode inside a cryogenic buffer gas cell. Here, we further explore the flexible capabilities of this infrastructure. We show that we can greatly increase the collective coupling strength of the molecular ensemble to the cavity by increasing the intracavity CH4 number density. In doing so, we can tune from the single-mode coupling regime to a multimode coupling regime in which many nested polaritonic states arise as the Rabi splitting approaches the cavity mode spacing. We explore polariton formation for cavity geometries of varying length, finesse, and mirror radius of curvature. We also report a proof-of-principle demonstration of rovibrational gas-phase polariton formation at room temperature. This experimental flexibility affords a great degree of control over the properties of molecular polaritons and opens up a wider range of simple molecular processes to future interrogation under strong cavity-coupling. We anticipate that ongoing work in gas-phase polaritonics will facilitate convergence between experimental results and theoretical models of cavity-altered chemistry and physics. [ABSTRACT FROM AUTHOR]

Metasurface holography is a significant technology for the development of ultrathin optical devices. Multichannel holography has received close attention due to its applications in increasing information capacity and optical secret sharing. However, existing design methods for multichannel holography mainly focus on interleaved metasurface imaging in the vertical direction, which will inevitably suffer from the unexpected crosstalk affecting imaging quality. This work presents noninterleaved spin-selective metasurfaces by combining the geometric phase and the propagating phase. It can achieve independent phase control on two orthogonal circular polarizations and image at the desired angle. As a proof-of-concept, two broadband plasmonic metasurfaces are designed for multichannel holographic imaging in the near-infrared band (800–1200 nm). When two orthogonal circularly polarized waves are normally incident, the first plasmonic metasurface displays two different holograms in the vertical direction, thus achieving dual-channel imaging, and the second plasmonic metasurface can make two holograms deflected to the desired angle. It means that these two holograms can be displayed without overlapping for a linearly polarized wave, and the orientable three-channel holographic imaging is realized. Our work provides a general and compact scheme for multichannel orientable holographic imaging. [ABSTRACT FROM AUTHOR]

It has been demonstrated previously that electrons interact differently with chiral molecules depending on their polarization. For enantiomeric pure monolayers of heptahelicene, opposite asymmetries in spin polarization were reported and attributed to the so-called chirality-induced spin selectivity effect. However, these promising proof-of-concept photoemission experiments lack the angular and energy resolution that could provide the necessary insights into the mechanism of this phenomenon. In order to fill in the missing gaps, we provide a detailed spin- and angle-resolved photoemission spectroscopy study of heptahelicene layers on a Cu(111) substrate. Throughout the large accessible energy and angle range, no chirality induced spin asymmetry in photoemission could be observed. Possible reasons for the absence of signatures of the spin-dependent electron transmission through the chiral molecular layer are briefly discussed. [ABSTRACT FROM AUTHOR]

The basis-set correction method based on density-functional theory consists in correcting the energy calculated by a wave-function method with a given basis set by a density functional. This basis-set correction density functional incorporates the short-range electron correlation effects missing in the basis set. This results in accelerated basis convergences of ground-state energies to the complete-basis-set limit. In this work, we extend the basis-set correction method to a linear-response formalism for calculating excited-state energies. We give the general linear-response equations as well as the more specific equations for configuration-interaction wave functions. As a proof of concept, we apply this approach to the calculations of excited-state energies in a one-dimensional two-electron model system with harmonic potential and a Dirac-delta electron–electron interaction. The results obtained with full-configuration-interaction wave functions expanded in a basis of Hermite functions and a local-density-approximation basis-set correction functional show that the present approach does not help in accelerating the basis convergence of excitation energies. However, we show that it significantly accelerates basis convergences of excited-state total energies. [ABSTRACT FROM AUTHOR]

We present a novel framework for spin-adapted coupled cluster theory. The approach exploits the entanglement of an open-shell molecule with electrons in a non-interacting bath. Together, the molecule and the bath form a closed-shell system, and electron correlation can be included using the standard spin-adapted closed-shell coupled cluster formalism. A projection operator, which enforces conditions on the electrons in the bath, is used to obtain the desired state of the molecule. This entanglement coupled cluster theory is outlined, and proof-of-concept calculations for doublet states are reported. The approach is further extendable to open-shell systems with other values of the total spin. [ABSTRACT FROM AUTHOR]

Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations. [ABSTRACT FROM AUTHOR]

The integration of quantum processing units (QPUs) in a heterogeneous high-performance computing environment requires solutions that facilitate hybrid classical–quantum programming. Standards such as OpenCL facilitate the programming of heterogeneous environments, consisting of CPUs and hardware accelerators. This study presents an innovative method that incorporates QPU functionality into OpenCL, standardizing quantum processes within classical environments. By leveraging QPUs within OpenCL, hybrid quantum–classical computations can be sped up, impacting domains like cryptography, optimization problems, and quantum chemistry simulations. Using Portable Computing Language (Jääskeläinen et al. in Int J Parallel Program 43(5):752–785, 2014. https://doi.org/10.1007/s10766-014-0320-y) and the Qulacs library (Suzuki et al. in Quantum 5:559, 2021. https://doi.org/10.22331/q-2021-10-06-559), results demonstrate, for instance, the successful execution of Shor's algorithm (Nielsen and Chuang in Quantum computation and quantum information, 10th anniversary edn. Cambridge University Press, Cambridge, 2010), serving as a proof of concept for extending the approach to larger qubit systems and other hybrid quantum–classical algorithms. This integration approach bridges the gap between quantum and classical computing paradigms, paving the way for further optimization and application to a wide range of computational problems. [ABSTRACT FROM AUTHOR]

Summary: Background: The current management of metabolic dysfunction‐associated steatotic liver disease (MASLD) relies on lifestyle intervention. Prior studies have shown that nutritional wheat amylase trypsin inhibitors (ATI) activate toll‐like receptor 4 on intestinal myeloid cells to enhance intestinal and extra‐intestinal inflammation, including the promotion of murine MASLD, insulin resistance and liver fibrosis. Aims: We aimed to assess the impact of ATI (gluten)‐free diet in liver as well as metabolic parameters of biopsy‐proven MASLD patients. Methods: We performed a 6‐week, proof‐of‐concept 1:1 randomised controlled trial of an ATI‐free diet. The controls followed a balanced diet recommended by the German Nutrition Society. We assessed changes in controlled attenuation parameter (CAP), body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA‐IR). Patient‐reported outcomes were assessed by the CLDQ‐NASH questionnaire. Forty‐five patients were consecutively enrolled (21 in the intervention arm and 24 in the control arm). Results: Three patients from each arm discontinued the study. In the ATI‐free diet group, a significant decrease in BMI (p = 0.018), CAP (p = 0.018) and HOMA‐IR (p = 0.042) was observed at 6 weeks. The mean difference in CAP between the two arms at week 6 was 30.5 dB/m (p = 0.039), with a delta significantly higher in the ATI‐free diet group (p = 0.043). Only an ATI‐free diet could achieve a significant improvement in CLDQ‐NASH domains (p value for total scoring: 0.013). Conclusions: A short‐term ATI‐free diet leads to significant improvements in liver and metabolic parameters, as well as patient‐reported outcomes with good tolerability. A larger follow‐up study is justified to corroborate these findings. Clinical trial number: NCT04066400. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). Methods: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. Results: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. Conclusions: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection "lung". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a global health issue known to cause avoidable harm and death. Improvement in its prevention and management is therefore considered an important goal for the health-care sector. The work here aimed to develop a tool which could be used to robustly and reliably measure, monitor, and compare the effectiveness of health-care interventions related to AKI across the Welsh NHS, a mechanism which did not exist previously. Methods: Using serum creatinine (SCr) as a biomarker for AKI and a validated national data-set collected from the all Wales Laboratory Information Management System, work involved applying Donabedian's framework to develop indicators with which to measure outcomes related to AKI, and exploring the potential of statistical process control (SPC) techniques for analysing data on these indicators. Results: Rate of AKI incidence and 30-day AKI-associated mortality are proposed as valid, feasible indicators with which to measure the effectiveness of health-care interventions related to AKI. The control chart, funnel plot, and Pareto chart are proposed as appropriate, robust SPC techniques to analyse and visualise variation in AKI-related outcomes. Conclusions: This work demonstrates that routinely collected large SCr data offer a significant opportunity to monitor and therefore inform improvement in patient outcomes related to AKI. Moreover, while this work concerns utilisation of SCr data for improvement in AKI strategies, it is a proof of concept which could be replicated for other routinely collected clinical laboratory data, to improve the prevention and/or management of the conditions to which they relate. [ABSTRACT FROM AUTHOR]

Background: Today, with wars raging in Ukraine and the Middle East, the demand for blood is high. Despite this, few companies produce the necessary equipment to draw, store, and transfuse whole blood. This study evaluated the safety and performance of a 3D printed bottle cap in conjunction with a water bottle and some available consumables to draw and store fresh whole blood. Study Design and Methods: Bags of saline, and freshly donated whole blood, was transferred to the water bottle through a 3D printed bottle cap and stored for 72 h. An identical setup, transferring saline to a Terumo blood collection bag was used as control. Performance and safety were evaluated by calculating infusion rate and observing for backflow, respectively. The blood was also tested for hemolysis and bacterial growth at four sampling points. Results: The cap‐and‐bottle setup was faster than control in terms of flow rate when transferring saline (1.53 vs. 1.81 mL/s, p <.001), and non‐inferior to saline control when transfusing blood (1.53 vs. 1.49 mL/s, p =.641). We did not observe any risks of causing the donor iatrogenic harm, and there was no evidence of increased hemolysis. However, there were traces of bacterial contamination in three of six bottles. Conclusion: This study indicates that drawing blood is both feasible and safe, utilizing a 3D printed cap and bottle setup. Flow rate was faster than control, and mechanical properties of the blood were not affected. We were unable to determine the source of bacterial contamination in the blood. [ABSTRACT FROM AUTHOR]

The reconfiguration of electrical distribution systems has been addressed in numerous scientific studies. Thus, several techniques and models are considered, especially to reduce electrical losses and improve the voltage profile. However, it is clear that even with the increase in research, which has been accentuated since the last decade, the locational pricing and the transmission costs allocation is little explored. In this regard, the proposed method is a distribution system reconfiguration (DSR) optimization problem focused on minimizing the use of the transmission system. In order to validate the meta‐heuristic employed for the DSR, the IEEE 33 and 69 node test systems are used as a proof of concept. In addition, case studies with four substations, three different transmission cost allocation techniques, and transmission system capacity scenarios are analyzed. Numerical results showed an important transmission expansion deferral with consequent decrease in overall costs compared to the classic DSR. The transmission network use of system (TNUoS) charges can play a crucial role in reducing the total cost of the electrical system, promoting distributors to change their feeder patterns so that a larger share of loads access substations with lower charges. [ABSTRACT FROM AUTHOR]

Background: Low self-confidence in patients with psychosis is common. This can lead to higher symptom severity, withdrawal from activities, and low psychological well-being. There are effective psychological techniques to improve positive self-beliefs but these are seldom provided in psychosis services. With young people with lived experience of psychosis we developed a scalable automated VR therapy to enhance positive-self beliefs. Aims: The aim was to conduct a proof of concept clinical test of whether the new VR self-confidence therapy (Phoenix) may increase positive self-beliefs and psychological well-being. Method: Twelve young patients with non-affective psychosis and with low levels of positive self-beliefs participated. Over 6 weeks, patients were provided with a stand-alone VR headset so that they could use Phoenix at home and were offered weekly psychologist meetings. The outcome measures were the Oxford Positive Self Scale (OxPos), Brief Core Schema Scale, and Warwick-Edinburgh Well-being Scale (WEMWBS). Satisfaction, adverse events and side-effects were assessed. Results: Eleven patients provided outcome data. There were very large end-of-treatment improvements in positive self-beliefs (OxPos mean difference = 32.3; 95% CI: 17.3, 47.3; Cohen's d =3.0) and psychological well-being (WEMWBS mean difference = 11.2; 95% CI: 8.0, 14.3; Cohen's d =1.5). Patients rated the quality of the VR therapy as: excellent (n =9), good (n =2), fair (n =0), poor (n =0). An average of 5.3 (SD =1.4) appointments were attended. Conclusions: Uptake of the VR intervention was high, satisfaction was high, and side-effects extremely few. There were promising indications of large improvements in positive self-beliefs and psychological well-being. A randomized controlled clinical evaluation is warranted. [ABSTRACT FROM AUTHOR]

Personalized educational interventions have been shown to facilitate successful and inclusive statistics, mathematics, and data science (SMDS) in higher education through timely and targeted reduction of heterogeneous training disparities caused by years of cumulative, structural challenges in contemporary educational systems. However, the burden on the institutions and instructors to provide personalized training resources to large groups of students is also formidable, and often unsustainable. We present Individualized Pathways and Resources to Adaptive Control Theory-Inspired Scientific Education (iPRACTISE), a free, publicly available web app that serves as a tool to facilitate personalized trainings on SMDS and related topics through provision of personalized training recommendations as informed by computerized assessments and individuals' training preferences. We describe the resources available in iPRACTISE, and some proof-of-concept evaluation results from deploying iPRACTISE to supplement in-person and online classroom teaching in real-life settings. Strengths, practical difficulties, and potentials for future applications of iPRACTISE to crowdsource and sustain personalized SMDS education are discussed. [ABSTRACT FROM AUTHOR]

Dissection of neural circuitry underlying behaviors is a central theme in neurobiology. We have previously proposed the concept of chemoconnectome (CCT) to cover the entire chemical transmission between neurons and target cells in an organism and created tools for studying it (CCTomics) by targeting all genes related to the CCT in Drosophila. Here we have created lines targeting the CCT in a conditional manner after modifying GFP RNA interference, Flp-out, and CRISPR/Cas9 technologies. All three strategies have been validated to be highly effective, with the best using chromatin-peptide fused Cas9 variants and scaffold optimized sgRNAs. As a proof of principle, we conducted a comprehensive intersection analysis of CCT genes expression profiles in the clock neurons, uncovering 43 CCT genes present in clock neurons. Specific elimination of each from clock neurons revealed that loss of the neuropeptide CNMa in two posterior dorsal clock neurons (DN1ps) or its receptor (CNMaR) caused advanced morning activity, indicating a suppressive role of CNMa-CNMaR on morning anticipation, opposite to the promoting role of PDF-PDFR on morning anticipation. These results demonstrate the effectiveness of conditional CCTomics and its tools created here and establish an antagonistic relationship between CNMa-CNMaR and PDF-PDFR signaling in regulating morning anticipation. [ABSTRACT FROM AUTHOR]

Experiments as Code (ExaC) is a concept for reproducible, auditable, debuggable, reusable, & scalable experiments. Experiments are a crucial tool to understand Human-Building Interactions (HBI) and build a coherent theory around it. However, a common concern for experiments is their auditability and reproducibility. Experiments are usually designed, provisioned, managed, and analyzed by diverse teams of specialists (e.g., researchers, technicians, engineers) and may require many resources (e.g., cloud infrastructure, specialized equipment). Although researchers strive to document experiments accurately, this process is often lacking. Consequently, it is difficult to reproduce these experiments. Moreover, when it is necessary to create a similar experiment, the "wheel is very often reinvented". It appears easier to start from scratch than trying to reuse existing work. Thus valuable embedded best practices and previous experiences are lost. In behavioral studies, such as in HBI, this has contributed to the reproducibility crisis. To tackle these challenges, we propose the ExaC paradigm, which not only documents the whole experiment, but additionally provides the automation code to provision, deploy, manage, and analyze the experiment. To this end, we define the ExaC concept, provide a taxonomy for the components of a practical implementation, and provide a proof of concept with an HBI desktop VR experiment that demonstrates the benefits of its "as code" representation, that is, reproducibility, auditability, debuggability, reusability, & scalability. [ABSTRACT FROM AUTHOR]

Defining the exact histological features of salivary gland malignancies before treatment remains an unsolved problem that compromises the ability to tailor further therapeutic steps individually. Radiomics, a new methodology to extract quantitative information from medical images, could contribute to characterizing the individual cancer phenotype already before treatment in a fast and non-invasive way. Consequently, the standardization and implementation of radiomic analysis in the clinical routine work to predict histology of salivary gland cancer (SGC) could also provide improvements in clinical decision-making. In this study, we aimed to investigate the potential of radiomic features as imaging biomarker to distinguish between high grade and low-grade salivary gland malignancies. We have also investigated the effect of image and feature level harmonization on the performance of radiomic models. For this study, our dual center cohort consisted of 126 patients, with histologically proven SGC, who underwent curative-intent treatment in two tertiary oncology centers. We extracted and analyzed the radiomics features of 120 pre-therapeutic MRI images with gadolinium (T1 sequences), and correlated those with the definitive post-operative histology. In our study the best radiomic model achieved average AUC of 0.66 and balanced accuracy of 0.63. According to the results, there is significant difference between the performance of models based on MRI intensity normalized images + harmonized features and other models (p value < 0.05) which indicates that in case of dealing with heterogeneous dataset, applying the harmonization methods is beneficial. Among radiomic features minimum intensity from first order, and gray level-variance from texture category were frequently selected during multivariate analysis which indicate the potential of these features as being used as imaging biomarker. The present bicentric study presents for the first time the feasibility of implementing MR-based, handcrafted radiomics, based on T1 contrast-enhanced sequences and the ComBat harmonization method in an effort to predict the formal grading of salivary gland carcinoma with satisfactory performance. [ABSTRACT FROM AUTHOR]

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate. [ABSTRACT FROM AUTHOR]

The controlled liberation of molecules from a constructed framework is a subject of profound interest across various chemical fields. It allows for the masking of a molecule's properties and precise deployment upon a single controllable release event. While numerous methodologies have been developed for amines, alcohols, and thiols, approaches for utilising amides as payload‐release handles are still in their early stages of development, despite the prevalence of amides in therapeutic compounds and materials. Herein, is presented a comprehensive strategy for the controlled and selective release of a diverse range of amides with stable linkers. The versatility of this approach is demonstrated by its successful application in the targeted release of various amide‐containing drugs in their natural form via the use of commonly used trigger motifs, such as dipeptides or glycosides. As a proof of concept, the FDA‐approved antibiotic linezolid has been successfully converted into a prodrug form and released selectively only in the presence of the trigger event. Significantly, in its prodrug state, no activity against Mycobacterium tuberculosis was exhibited. Linezolid's full potential was achieved only upon controlled release, where an equipotent efficacy to the free linezolid control was demonstrated, thus emphasising the immense potential of this method. [ABSTRACT FROM AUTHOR]

Concentration gradient generation and mixed combinations of multiple solutions are of great value in the field of biomedical research. However, existing concentration gradient generators for single or two-drug solutions cannot simultaneously achieve multiple concentration gradient formations and mixed solution combinations. Furthermore, the whole system was huge, and required expensive auxiliary equipment, which may lead to complex operations. To address this problem, we devised a novel 3D microchannel network design, which is capable of creating all the desired mixture combinations and concentration gradients of given small amounts of the input solutions. As a proof of concept, the device we presented was verified by both colorimetric and fluorescence detection methods to test the efficiency. This can enable the implementation of one to three solutions with no driving pump and facilitate unique multiple types of more concentration gradients and mixture combinations in a single operation. We envision that this will be a promising candidate for the development of simplified methods for screening of the appropriate concentration and combination, such as various drug screening applications. [ABSTRACT FROM AUTHOR]

The field of bioorthogonal chemistry is rapidly growing, presenting successful applications of organic and transition metal‐catalysed reactions in cells and living systems (in vivo). The development of such reactions typically proceeds through many iterative steps focused on biocompatibility and fast reaction kinetics to ensure product formation. However, obtaining kinetic data, even under simulated biological (biomimetic) conditions, remains a challenge due to substantial concentrations of salts and biomolecules hampering the use of typically employed solution‐phase analytical techniques. In this study, we explored the suitability of gas evolution as a probe to study kinetics under biomimetic conditions. As proof of concept, we show that the progress of two transition metal‐catalysed bioorthogonal chemical reactions can be accurately monitored, regardless of the complexity of the medium. As such, we introduce a protocol to gain more insight into the performance of a catalytic system under biomimetic conditions to further progress iterative catalyst development for in vivo applications. [ABSTRACT FROM AUTHOR]

The investigation of reaction mechanisms is a complex task that usually requires the use of several techniques. To obtain as much information as possible on the reaction and any intermediates – possibly invisible to one technique – the combination of techniques is a solution. In this work we present a new setup for combined UV/Vis and NMR spectroscopy and compare it to an established alternative. The presented approach allows a versatile usage of different commercially‐available components like mirrors and fiber bundles as well as different fixed pathlengths according to double transmission or single transmission measurements. While a previous approach is based on a dip‐probe setup for conventional NMR probes, the new one is based on a micro‐Helmholtz coil array (LiquidVoxel™). This makes the use of rectangular cuvettes possible, which ensure well‐defined pathlengths allowing for quantification of species. Additionally, very low quantities of compound can be analyzed due to the microfabrication and small cuvette size used. As proof‐of‐principle this new setup for combined UV/Vis and NMR spectroscopy is used to examine a well‐studied photochromic system of the dithienylethene compound class. A thorough comparison of the pros and cons of the two setups for combined UV/Vis and NMR measurements is performed. [ABSTRACT FROM AUTHOR]

A general strategy for designing bi‐layer reflection‐transmission integrated dual‐mode metasurfaces is presented with flexible bandwidth control. The design of such metasurfaces is enlightened by introducing a cutting hole in the ground plane, which not only acts as a filter for reflection and transmission but also has an eloquent role for bandwidth control. For proof of concept, a bi‐layer metasurface consisting of split ring resonators (SRRs) is designed on the top side and I‐shaped resonators on both sides. The proper adjustment of ground cut/hole shifts the two co‐polarized resonances (initial resonances of the SRRs) close to each other, and in addition, converts wideband cross‐polarized reflection (in between the two initial co‐polarized resonances of SRR) to co‐polarized reflection. This results in a broadband response by shifting two co‐polarized resonances close to each other and converting cross‐polarized reflection into co‐polarized reflection. It is demonstrated that a simple SRR can be responsible for broadband (7.9–12 GHz) reflection while an I‐shaped structure is used for transmission with central frequency at 17.58 GHz with independent phase controls. To endorse the proposed strategy, a metasurface prototype is fabricated and tested for the generation of vortex beams and focusing. [ABSTRACT FROM AUTHOR]

In the current prevalent complex electromagnetic (EM) environment, intelligent methods for versatile and integrated control of EM waves using compact devices are both essential and challenging. These varied wave control objectives can at times conflict with one another, such as the need for broad absorption to remain inconspicuous, while also requiring enhanced backward scattering for highly reliable tracing and secure communication. To address these sophisticated challenges, a microwave‐frequency reconfigurable tri‐mode metasurface (RTMM) is introduced. The proposed innovation enables three distinct operational modes: broadband low observation, enhanced EM wave tracing, and backscatter communication over a wide‐angle range by simple control of the PIN diodes embedded in each meta‐atom. The proof‐of‐concept demonstration of the fabricated prototype verified the switchable tri‐mode performance of the RTMM. This proposed RTMM can be adapted to various applications, including EM shielding, target detection, and secure communication in complex and threatening EM environments, paving the way for environmentally‐adaptive EM wave manipulation. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry–induced sepsis. These mice featured persistent inflammatory responses and were effectively rescued by GC therapy. RNA sequencing analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients based on the status of RAI. [ABSTRACT FROM AUTHOR]

A primal quadratic simplex algorithm tailored to the optimization over the vertices of a polytope is presented. Starting from a feasible vertex, it performs either strictly improving or admissible non-deteriorating steps in order to determine a locally optimum basic feasible solution in terms of the quadratic objective function. The algorithm so generalizes over local improvement methods for according applications, including in particular quadratic optimization problems whose feasible solutions correspond to vertices of a 0-1 polytope. Computational experiments for unconstrained binary quadratic programs, maximum cut, and the quadratic assignment problem serve as a proof of concept and underline the importance of a pivoting rule that is able to accept at least a restricted class of degenerate steps. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data. Methods: The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies. Results: Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information. Conclusion: The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors. [ABSTRACT FROM AUTHOR]

A series of proof-of-concept models of polyoxomolybdates with different protonated disubstituted aniline counterions and the same β-Mo8O26 polyanion were synthesized to study the mechanism governing the formation of the intermolecular charge transfer (inter-CT) band. [ABSTRACT FROM AUTHOR]

Background: Biomarker discovery is a challenging task due to the massive search space. Quantum computing and quantum Artificial Intelligence (quantum AI) can be used to address the computational problem of biomarker discovery from genetic data. Method: We propose a Quantum Neural Networks architecture to discover genetic biomarkers for input activation pathways. The Maximum Relevance-Minimum Redundancy criteria score biomarker candidate sets. Our proposed model is economical since the neural solution can be delivered on constrained hardware. Results: We demonstrate the proof of concept on four activation pathways associated with CTLA4, including (1) CTLA4-activation stand-alone, (2) CTLA4-CD8A-CD8B co-activation, (3) CTLA4-CD2 co-activation, and (4) CTLA4-CD2-CD48-CD53-CD58-CD84 co-activation. Conclusion: The model indicates new genetic biomarkers associated with the mutational activation of CLTA4-associated pathways, including 20 genes: CLIC4, CPE, ETS2, FAM107A, GPR116, HYOU1, LCN2, MACF1, MT1G, NAPA, NDUFS5, PAK1, PFN1, PGAP3, PPM1G, PSMD8, RNF213, SLC25A3, UBA1, and WLS. We open source the implementation at: https://github.com/namnguyen0510/Biomarker-Discovery-with-Quantum-Neural-Networks. [ABSTRACT FROM AUTHOR]

Much of the information gleaned from observations of star-forming regions comes from the analysis of their molecular emission spectra, particularly in the radio regime. The time-consuming nature of fitting synthetic spectra to observations interactively for such line-rich sources, however, often results in such analysis being limited to data extracted from a single-dish observation or a handful of pixels from an interferometric observation. Yet, star-forming regions display a wide variety of physical conditions that are difficult, if not impossible, to accurately characterize with such a limited number of spectra. We have developed an automated fitting routine that visits every pixel in the field of view of an Atacama Large Millimeter/submillimeter Array (ALMA) data cube and determines the best-fit physical parameters, including excitation temperature and column densities, for a given list of molecules. In this proof-of-concept work, we provide an overview of the fitting routine and apply it to 0.″26, 1.1 km s−1 resolution ALMA observations of two sites of massive star formation in NGC 6334I. Parameters were found for 21 distinct molecules by generating synthetic spectra across 7.48 GHz of spectral bandwidth between 280 and 351 GHz. Spatial images of the derived parameters for each of the >8000 pixels are presented with special attention paid to the C2H4O2 isomers and their relative variations. We highlight the greater scientific utility of the column density and velocity images of individual molecules compared to traditional moment maps of single transitions. [ABSTRACT FROM AUTHOR]

Sixty years ago, Reddy, Devanatan, and Bockris performed the first in situ electrochemical ellipsometry experiment, which ushered in a new era in the study of electrochemistry, using optical spectroscopy. After six decades of development, electrochemical optical spectroscopy, particularly electrochemical vibrational spectroscopy, has advanced from a phase of immaturity with few methods and limited applications to a phase of maturity with excellent substrate generality and significantly improved resolutions. Here, we divide the development of electrochemical optical spectroscopy into four phases, focusing on the proof-of-concept of different electrochemical optical spectroscopy studies, the emergence of plasmonic enhancement-based electrochemical optical spectroscopic (in particular vibrational spectroscopic) methods, the realization of electrochemical vibrational spectroscopy on welldefined surfaces, and the efforts to achieve operando spectroelectrochemical applications. Finally, we discuss the future development trend of electrochemical optical spectroscopy, as well as examples of new methodology and research paradigms for operando spectroelectrochemistry. [ABSTRACT FROM AUTHOR]

Proof-of-concept of photonic lithotripsy in an in vitro setting and its ability to fragment the most common stone types is demonstrated. Effectiveness of different classes of photonic nanoparticles in fragmenting human stones is assessed. De-identified human stones were collected after institutional approval. Stones of a size range between 2–4 mm were rehydrated in simulated urine for 24 h. Stones were then coated with a solution of nanoparticles prior to activation with either a 785 nm or 1320 nm near-infrared energy source. Photonic lithotripsy achieved greater than 70% success rate in fragmentating calcium oxalate monohydrate stones using carbon-based nanoparticles for both near-infrared wavelengths. For gold-based nanoparticles, there was a similar success rate with the 785 nm wavelength but a significant decrease when using the 1320 nm wavelength energy source. All stones fragmented with the energy source at a distance ≥ 20 mm from the stone's surface. Limitations include the use of mixed-composition stones, a lack of complete stone immersion in liquid during treatment, and smaller stone size. Different classes of nanoparticles when excited with a near-infrared energy source can fragment common stone types in vitro. This technology has the potential to change the way we approach and treat patients with urolithiasis in a clinical setting. [ABSTRACT FROM AUTHOR]

The human skin virome, unlike commensal bacteria, is an under investigated component of the human skin microbiome. We developed a sensitive, quantitative assay to detect cutaneous human resident papillomaviruses (HPV) and polyomaviruses (HPyV) and we first used it to describe these viral populations at the skin surface of two patients with atopic dermatitis (AD) and psoriasis (PSO). We performed skin swabs on lesional and non-lesional skin in one AD and one PSO patient at M0, M1 and M3. After extraction, DNA was amplified using an original multiplex PCR technique before high throughput sequencing (HTS) of the amplicons (named AmpliSeq-HTS). Quantitative results were ultimately compared with monoplex quantitative PCRs (qPCRs) for previously detected viruses and were significantly correlated (R2 = 0.95, ρ = 0.75). Fifteen and 13 HPV types (mainly gamma and beta-HPVs) or HPyV species (mainly Merkel Cell Polyomavirus (MCPyV)) were detected on the skin of the AD and PSO patients, respectively. In both patients, the composition of the viral flora was variable across body sites but remained stable over time in non-lesional skin samples, mostly colonized with gamma-papillomaviruses. In lesional skin samples, beta-papillomaviruses and MCPyV were the major components of a viral flora more prone to vary over time especially with treatment and subsequent clinical improvement. We believe this method might be further used in extensive studies to further enhance the concept of an individual cutaneous viral fingerprint and the putative role of its alterations through various skin diseases and their treatments. [ABSTRACT FROM AUTHOR]

Grover's algorithm has been widely used for quantum key search to attack block ciphers with a quadratic speedup as compared to classical brute-force attacks and also used for evaluating the post-quantum security of block ciphers against quantum computer attack. But, this quantum key search on block ciphers has a high quantum circuit depth and AES-128 is still secure against such attack. In this paper, we introduce a method called the depth–measurement trade-off method that reduces the overall quantum circuit depth of quantum key search to attack block ciphers by increasing the number of measurements of the circuit. This method is to introduce dummy keys in the quantum circuit as part of the correct key. This will reduce both quantum circuit resource and quantum circuit depth. Based on this technique, the quantum circuit depth of AES-128 is less than 2 64 , while NIST suggested circuit depth should be greater than MAXDEPTH, which is 2 40 , 2 64 and 2 96 in order to resist the respective attacks. In addition, we also simulated the depth–measurement trade-off method on the reduced SIMON block cipher algorithm as a proof of concept. Furthermore, we also apply the depth–measurement technique on various block ciphers, for example AES, PRESENT, SIMON, GIFT, SPECK, RECTANGLE, LowMC, KNOT, PIPO, etc. [ABSTRACT FROM AUTHOR]

Visual and auditory stimuli are transmitted from the environment to sensory cortices with different timing, requiring the brain to encode when sensory inputs must be segregated or integrated into a single percept. The probability that different audiovisual (AV) stimuli are integrated into a single percept even when presented asynchronously is reflected in the construct of temporal binding window (TBW). There is a strong interest in testing whether it is possible to broaden or shrink TBW by using different neuromodulatory approaches that can speed up or slow down ongoing alpha oscillations, which have been repeatedly hypothesized to be an important determinant of the TBWs size. Here, we employed a web-based sensory entrainment protocol combined with a simultaneity judgment task using simple flash-beep stimuli. The aim was to test whether AV temporal acuity could be modulated trial by trial by synchronizing ongoing neural oscillations in the prestimulus period to a rhythmic sensory stream presented in the upper (∼12 Hz) or lower (∼8.5 Hz) alpha range. As a control, we implemented a nonrhythmic condition where only the first and the last entrainers were employed. Results show that upper alpha entrainment shrinks AV TBW and improves AV temporal acuity when compared with lower alpha and control conditions. Our findings represent a proof of concept of the efficacy of sensory entrainment to improve AV temporal acuity in a trial-by-trial manner, and they strengthen the idea that alpha oscillations may reflect the temporal unit of AV temporal binding. [ABSTRACT FROM AUTHOR]

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of −5.4 ± 0.55 and −6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide. [ABSTRACT FROM AUTHOR]

Bayesian phylogenetic methods offer various models that would be especially suitable in the reconstruction of textual traditions, but text-critical applications of phylogenetics to date have generally not taken advantage of these features. In this article, we offer a way forward for text-critical phylogenetics. On the side of theory, we highlight multiple Bayesian phylogenetic models and discuss their relevance to textual criticism. More practically, we show how TEI XML collations of textual traditions can be encoded to facilitate robust analyses using these models in BEAST 2, with the teiphy Python package mediating the conversion from TEI XML to BEAST XML. Finally, we give a proof of concept for this approach, showing that the results of BEAST 2 analyses of a sample collation of the Epistle to the Ephesians under different clock models cohere with established findings on the textual tradition of this work. [ABSTRACT FROM AUTHOR]

Modern glycoproteomics experiments require the use of search engines due to the generation of countless spectra. While these tools are valuable, manual validation of search engine results is often required for detailed analysis of glycopeptides as false-discovery rates are often not reliable for glycopeptide data. Near-isobaric mismatches are a common source of misidentifications for the popular glycopeptide-focused search engine pGlyco3.0, and in this technical note we share a strategy and script that improves the accuracy of the search utilizing two manually validated datasets of the glycoproteins CD16a and HIV-1 Env as proof-of-principle. [ABSTRACT FROM AUTHOR]

Background: After stroke, restoring safe, independent, and efficient walking is a top rehabilitation priority. However, in nearly 70% of stroke survivors asymmetrical walking patterns and reduced walking speed persist. This case series study aims to investigate the effectiveness of transcutaneous spinal cord stimulation (tSCS) in enhancing walking ability of persons with chronic stroke. Methods: Eight participants with hemiparesis after a single, chronic stroke were enrolled. Each participant was assigned to either the Stim group (N = 4, gait training + tSCS) or Control group (N = 4, gait training alone). Each participant in the Stim group was matched to a participant in the Control group based on age, time since stroke, and self-selected gait speed. For the Stim group, tSCS was delivered during gait training via electrodes placed on the skin between the spinous processes of C5–C6, T11–T12, and L1–L2. Both groups received 24 sessions of gait training over 8 weeks with a physical therapist providing verbal cueing for improved gait symmetry. Gait speed (measured from 10 m walk test), endurance (measured from 6 min walk test), spatiotemporal gait symmetries (step length and swing time), as well as the neurophysiological outcomes (muscle synergy, resting motor thresholds via spinal motor evoked responses) were collected without tSCS at baseline, completion, and 3 month follow-up. Results: All four Stim participants sustained spatiotemporal symmetry improvements at the 3 month follow-up (step length: 17.7%, swing time: 10.1%) compared to the Control group (step length: 1.1%, swing time 3.6%). Additionally, 3 of 4 Stim participants showed increased number of muscle synergies and/or lowered resting motor thresholds compared to the Control group. Conclusions: This study provides promising preliminary evidence that using tSCS as a therapeutic catalyst to gait training may increase the efficacy of gait rehabilitation in individuals with chronic stroke. Trial registration NCT03714282 (clinicaltrials.gov), registration date: 2018-10-18. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC. However, the role of PD-L1 as a liquid biomarker has not yet been fully explored. Herein, we analyze urine levels of PD-L1 in mRCC patients before and after either ICI therapy or surgical intervention, as well as in a series of patients with treatment-naïve RCC. Patients and Methods: The mid-stream urine of patients with mRCC (n = 4) or treatment-naïve RCC, i.e., prior to surgery from two centers (cohort I, n = 49: cohort II, n = 29) was analyzed for PD-L1 by ELISA. The results from cohort I were compared to a control group consisting of patients treated for non-malignant urologic diseases (n = 31). In the mRCC group, urine PD-L1 levels were measured before and after tumor nephrectomy (n = 1) or before and after ICI therapy (n = 3). Exosomal PD-L1 in the urine was analyzed in selected patients by immunoblotting. Results: A strong decrease in urine PD-L1 levels was found after tumor nephrectomy or following systemic treatment with ICIs. In patients with treatment-naïve RCC (cohort I), urine PD-L1 levels were significantly elevated in the RCC group in comparison to the control group (median 59 pg/mL vs. 25.7 pg/mL, p = 0.011). PD-L1 urine levels were found to be elevated, in particular, in low-grade RCCs in cohorts I and II. Exosomal PD-L1 was detected in the urine of a subset of patients. Conclusion: In this proof-of-concept study, we show that PD-L1 can be detected in the urine of RCC patients. Urine PD-L1 levels were found to correlate with the treatment response in mRCC patients and were significantly elevated in treatment-naïve RCC patients. [ABSTRACT FROM AUTHOR]

Background: Lateral epicondylitis (LE) causes lateral elbow pain due to the overuse of the common extensor tendon. Several therapies have been proposed for pain relief and functional recovery, including physical therapy, minimally invasive injection approaches, and physical agent modalities such as laser therapy. Methods: Our study evaluates the impact of high-power laser therapy (HPLT) on pain and functioning. The HPLT protocol consists of 10 daily sessions using a LASERIX PRO device. The healthy elbow of each participant was also considered as a control group. The outcomes assessed were the Numerical Rating Scale (NRS) for pain, QuickDASH questionnaire for functionality, and shear wave velocity (SWS) through ultrasonography. Assessments were conducted at baseline (T0), post-treatment (T1), and 2-week follow-up (T2). Results: Sixteen participants (81.2% male, mean age 40.4 ± 5.53 years) completed the study. Post-treatment, pain significantly decreased (NRS: T0 6.13 ± 0.96; T1 2.75 ± 1.69; p <  0.001), functionality improved (QuickDASH: T0 69.88 ± 10.75; T1 41.20 ± 3.78; p < 0.001), and shear wave velocity increased (SWS (m/s): T0 1.69 ± 0.35; T1 2.56 ± 0.36; p <  0.001). Conclusions: At the 2-week follow-up, pain relief was maintained, and shear wave velocity showed no further significant change. Shear wave velocity assessments might be considered a useful diagnostic tool. However, further research is needed to support the role of HPLT and shear wave velocity in the rehabilitation management of LE. [ABSTRACT FROM AUTHOR]

The insecticidal property of ring C-seco limonoids has been discovered empirically and the target protein identified, but, to date, the molecular mechanism of action has not been described at the atomic scale. We elucidate on computational grounds whether nine C-seco limonoids present sufficiently high affinity to bind specifically with the putative target enzyme of the insects (ecdysone 20-monooxygenase). To this end, 3D models of ligands and the receptor target were generated and their interaction energies estimated by docking simulations. As a proof of concept, the tetrahydro-isoquinolinyl propenamide derivative QHC is the reference ligand bound to aldosterone synthase in the complex with PDB entry 4ZGX. It served as the 3D template for target modeling via homology. QHC was successfully docked back to its crystal pose in a one-digit nanomolar range. The reported experimental binding affinities span over the nanomolar to lower micromolar range. All nine limonoids were found with strong affinities in the range of −9 < ΔG < −13 kcal/mol. The molt hormone ecdysone showed a comparable ΔG energy of −12 kcal/mol, whereas −11 kcal/mol was the back docking result for the liganded crystal 4ZGX. In conclusion, the nine C-seco limonoids were strong binders on theoretical grounds in an activity range between a ten-fold lower to a ten-fold higher concentration level than insecticide ecdysone with its known target receptor. The comparable or even stronger binding hints at ecdysone 20-monooxygenase as their target biomolecule. Our assumption, however, is in need of future experimental confirmation before conclusions with certainty can be drawn about the true molecular mechanism of action for the C-seco limonoids under scrutiny. [ABSTRACT FROM AUTHOR]

Background: A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer's disease (AD) in which a given outcome is most relevant (i.e., has the greatest risk of degradation). The framework guides the selection of endpoints measuring outcomes relevant within a target AD population. Here, a proof of concept is presented via post-hoc analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012). Objective: To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized 'target' stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS). Methods: Three endpoints were tested: ADAS-Cog 12, ADCS-ADL, and QoL-AD. The magnitude of treatment efficacy was hypothesized to be maximized in the target stages of mild, mild-to-moderate, and very mild AD, respectively, compared to the full analysis set (FAS) and non-target stages. Results: For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (–4.0, p = 0.0760) compared to target stage and FAS. For ADCS-ADL and QoL-AD, the magnitude of treatment efficacy was largest in the target stage (14.2, p = 0.0003; 2.4, p < 0.0001, respectively) compared to non-target stage and FAS. Conclusions: Findings indicated that evaluating endpoints in the most relevant AD stage can increase the magnitude of the observed treatment efficacy. Evidence provides preliminary proof of concept for the endpoint staging framework. [ABSTRACT FROM AUTHOR]

Liguleless mutants produce defective ligules and auricles and, consequently, have more upright leaves than their ligulate counterparts, making them useful genetic material for plant architectural studies. Besides, owing to the recessive nature and amenability of the liguleless trait to phenotyping at the seedling stage, liguleless mutants are popularly used for 'proof‐of‐concept' demonstration and assessment of haploid induction rate (HIR) of haploid inducer lines (HILs) in maize. The commonly used liguleless testers in maize are of temperate origin and are challenging to use and maintain under tropical/sub‐tropical conditions. In the present study, liguleless lines (V 601, V 602, V 603 and V 604) derived from crosses between agronomically superior locally adapted tropical ligulate lines (V 407 and CM 152) and liguleless donors of temperate origin (PDH‐3 and PDH‐8) were evaluated for different agro‐morphological traits. Liguleless line V 602 was also used as a tester to assess the HIR of haploid inducer line EC937890 (CIM2GTAILP2). The results showed a mean HIR of 12.42% for EC937890, consistent with the HIR reported in other studies, thus demonstrating the efficacy of V 602 as a tester for determining HIR. The agronomically superior liguleless maize lines reported in this study will, therefore, be a valuable resource for leaf architectural studies, assessment of HIR of candidate HILs and maintenance of high HIR in the HILs presently in wide use in the doubled haploid (DH) programmes. Additionally, these genetic stocks carry the liguleless trait in genetic backgrounds with known heterotic affinity with early maturity Indian public maize germplasm and, therefore, can be used directly as parents in hybrid development programmes. [ABSTRACT FROM AUTHOR]

Recent advances in the area of the Internet of Things shows that devices are usually resource-constrained. To enable advanced applications on these devices, it is necessary to enhance their performance by leveraging external computing resources available in the network. This work presents a study of computational platforms to increase the performance of these devices based on the Mobile Cloud Computing (MCC) paradigm. The main contribution of this paper is to research the advantages and possibilities of architectures with multiple offloading options. To this end, a review of architectures that use a combination of the computing layers in the available infrastructure to perform this paradigm and outsource processing load is presented. In addition, a proof-of-concept application is introduced to demonstrate its realization along all the network layers. The results of the simulations confirm the high flexibility to offload numerous tasks using different layers and the ability to overcome unfavorable scenarios. [ABSTRACT FROM AUTHOR]

Introduction Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment and rapid antimicrobial susceptibility testing (AST) would be valuable. We have developed a rapid and accurate flow cytometry method (FCM) for AST of gonococci. Methods The 2016 WHO gonococcal reference strains, and WHO Q, R and S (n  = 17) were tested against seven clinically relevant antibiotics (ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and gentamicin). After 4.5 h incubation of inoculated broth, the fluorescent dye Syto™ 9 was added, followed by FCM analysis. After gating, the relative remaining population of gonococci, compared with unexposed growth control samples, was plotted against antimicrobial concentration, followed by non-linear curve regression analysis. Furthermore, the response at one single concentration/tested antibiotic was evaluated with the intention to use as a screening test for detection of resistant gonococci. Results A dose-dependent response was seen in susceptible isolates for all tested antimicrobials. There was a clear separation between susceptible/WT and resistant/non-WT isolates for ceftriaxone, cefixime, spectinomycin, ciprofloxacin and tetracycline. In contrast, for azithromycin, only high-level-resistant isolates were distinguished, while resistant isolates with MICs of 4 mg/L were indistinguishable from WT (MIC ≤ 1 mg/L) isolates. For gentamicin, all tested 17 isolates were WT and FCM analysis resulted in uniform dose–response curves. Using a single antibiotic concentration and a 50% remaining cell population cut-off, the overall sensitivity and specificity for resistance detection were 93% and 99%, respectively. Conclusions By providing results in <5 h for gonococcal isolates, FCM-based AST can become a rapid screening method for antimicrobial resistance or antimicrobial susceptibility in gonococci. [ABSTRACT FROM AUTHOR]