Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

Non-destructive classification of unlabeled cells: Combining an automated benchtop magnetic resonance scanner and artificial intelligence.

In order to treat degenerative diseases, the importance of advanced therapy medicinal products has increased in recent years. The newly developed treatment strategies require a rethinking of the appropriate analytical methods. Current standards are missing the complete and sterile analysis of the product of interest to make the drug manufacturing effort worthwhile. They only consider partial areas of the sample or product while also irreversibly damaging the investigated specimen. Two-dimensional T1 / T2 MR relaxometry meets these requirements and is therefore a promising in-process control during the manufacturing and classification process of cell-based treatments. In this study a tabletop MR scanner was used to perform two-dimensional MR relaxometry. Throughput was increased by developing an automation platform based on a low-cost robotic arm, resulting in the acquisition of a large dataset of cell-based measurements. Two-dimensional inverse Laplace transformation was used for post-processing, followed by data classification performed with support vector machines (SVM) as well as optimized artificial neural networks (ANN). The trained networks were able to distinguish non-differentiated from differentiated MSCs with a prediction accuracy of 85%. To increase versatility, an ANN was trained on 354 independent, biological replicates distributed across ten different cell lines, resulting in a prediction accuracy of up to 98% depending on data composition. The present study provides a proof of principle for the application of T1 / T2 relaxometry as a non-destructive cell classification method. It does not require labeling of cells and can perform whole mount analysis of each sample. Since all measurements can be performed under sterile conditions, it can be used as an in-process control for cellular differentiation. This distinguishes it from other characterization techniques, as most are destructive or require some type of cell labeling. These advantages highlight the technique's potential for preclinical screening of patient-specific cell-based transplants and drugs.

Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile.

BACKGROUND: Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials. RESULTS: We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators. CONCLUSIONS: Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.

Probing the Ni(OH)2 Precursor for LiNiO2 at the Atomic Scale: Insights into the Origin of Structural Defect in a Layered Cathode Active Material.

In lithium ion batteries (LIBs), the layered cathode materials of composition LiNi1- x - y Cox Mny O2  are critical for achieving high energy densities. A high nickel content (>80%) provides an attractive balance between high energy density, long lifetime, and low cost. Consequently, Ni-rich layered oxides cathode active materials (CAMs) are in high demand, and the importance of LiNiO2 (LNO) as limiting case, is hence paramount. However, achieving perfect stoichiometry is a challenge resulting in various structural issues, which successively impact physicochemical properties and result in the capacity fade of LIBs. To better understand defect formation in LNO, the role of the Ni(OH)2  precursor morphology in the synthesis of LNO requires in-depth investigation. By employing aberration-corrected scanning transmission electron microscopy, electron energy loss spectroscopy, and precession electron diffraction, a direct observation of defects in the Ni(OH)2  precursor preparedis reported and the ex situ structural evolution from the precursor to the end product is monitored. During synthesis, the layered Ni(OH)2  structure transforms to partially lithiated (non-layered) NiO and finally to layered LNO. The results suggest that the defects observed in commercially relevant CAMs originate to a large extent from the precursors, hence care must be taken in tuning the co-precipitation parameters to synthesize defect-free Ni-rich layered oxides CAMs.

Deterministic switching of a perpendicularly polarized magnet using unconventional spin-orbit torques in WTe2.

Spin-orbit torque (SOT)-driven deterministic control of the magnetic state of a ferromagnet with perpendicular magnetic anisotropy is key to next-generation spintronic applications including non-volatile, ultrafast and energy-efficient data-storage devices. However, field-free deterministic switching of perpendicular magnetization remains a challenge because it requires an out-of-plane antidamping torque, which is not allowed in conventional spin-source materials such as heavy metals and topological insulators due to the system's symmetry. The exploitation of low-crystal symmetries in emergent quantum materials offers a unique approach to achieve SOTs with unconventional forms. Here we report an experimental realization of field-free deterministic magnetic switching of a perpendicularly polarized van der Waals magnet employing an out-of-plane antidamping SOT generated in layered WTe2, a quantum material with a low-symmetry crystal structure. Our numerical simulations suggest that the out-of-plane antidamping torque in WTe2 is essential to explain the observed magnetization switching.

The influence of political ideology on clinical trial knowledge, invitation, and participation among adults in the United States.

BACKGROUND: Clinical trials remain a critical component of medical innovation. Evidence suggests that individuals' political ideologies may impact their health behaviors. However, there is a paucity of literature examining the relationship between political ideologies and clinical trial knowledge and participation. METHODS: Study data were derived from Health Information National Trends Survey 5 Cycle 4 (n = 3300), which was conducted from February to June 2020. We used participants' characteristics to estimate the prevalence of clinical trial knowledge and participation. We used multivariable logistic regressions to investigate whether political ideology had a significant impact on clinical trial knowledge and participation. Jack-knife replicate weights were applied for population-level estimates. RESULTS: Most participants were White (64.2%), earned above US$50,000 (62.4%), and lived in urban areas (88.0%). About 59.2% reported having some knowledge of clinical trials, and only 8.9% had ever been invited to participate in clinical trials. A total of 37.0%, 29.5%, and 33.5% of the population endorsed moderate, liberal, and conservative political viewpoints respectively. In the adjusted logistic regression analysis, compared to conservatives, liberals (adjusted odds ratio, 1.92; 95% confidence interval, 1.31-2.80) and moderates (adjusted odds ratio, 1.43; 95% confidence interval, 1.09-1.88) had significantly greater odds of having knowledge of clinical trials. Also, liberals had higher odds of receiving invitations to participate in clinical trials (odds ratio, 1.76; 95% confidence interval, 1.08-2.85; p = 0.023) and greater odds of trial participation (odds ratio, 3.90; 95% confidence interval, 1.47-10.33; p = 0.007) compared to moderates. CONCLUSIONS: The mechanism underlying the higher rates of clinical trial invitations to liberals is unclear and requires further comprehensive investigation. Similarly, further qualitative studies are needed to understand the attributes that promote knowledge and increased likelihood of clinical trial participation among liberals. This will provide crucial insight to help design interventions that further involve conservatives and moderates in clinical trials and scientific enterprise.

Application of Fuzzy Composite Programming in a Questionnaire as a Methodological Test to Study the Effect of Reservoir Management on Social Interests-A Survey Based on Two Case Studies in Southern Germany.

To understand the concerns, approvals and disapprovals of expert opinions about managerial issues from around reservoirs this study uses the approach of Fuzzy Composite Programming (FCP) in direct questionnaires to parameterize and rate a set of indicators with statements about managerial issues concerning societal implications by the responding experts. The personal ratings get summarized in four different layers and converted into one final numerical value which will be in the range of 0 as the absolute disapproval of the indicators and 1 as the absolute approval of the indicators. The FCP approach thereby rates the individual indicator, secondly the indicator category, thirdly the compensational factor and fourthly the dimensions of sustainability. This facilitates a rapid comparison of results of rather complicated sets of pre-set indicators in topics reaching from legal issues to societal concerns in one final numerical value to identify crucial topics and start open debates. This study was carried out as a methodological test at two water reservoirs in southern Germany. The results show a general possibility of using a rather retrospect methodology towards current ratings of experts in the field of reservoir management. 10 respondents answered the FCP questionnaires, 5 at each study site. The scores of the calculation showed a higher level of positive connection in the case of the Schwarzenbachtalsperre (SBT) with a score of 0.77, compared to a score of 0.54 in the case of the Franconian Lake District (FLD). Apart from the pure numerical scores, FCP can show conflicting issues and possible compromise solutions between the different stakeholders, in/based on the individual ratings. The findings could help reach a more sustainable management of water resources that includes all stakeholders, by pointing out debatable implications.

Nutritional, textural and sensory properties of lasagna dough containing air yam, a non-conventional edible plant.

The incorporation of non-conventional edible plants into gluten-free food products shows potential and the ability to increase nutritional properties. Therefore, the aim of this study was to develop a gluten-free air yam-based lasagna dough and to evaluate the nutritional, textural, and sensory properties. First, the air yam flour was obtained by drying the tubers at 55 °C for 16 h and then, mixed with the water and egg powder, it constituted the lasagna dough. The nutritional composition and bioaccessible mineral content of air yam flour and lasagna dough were evaluated, as well as the texture, microbiological and sensory properties of the lasagna dough. The results indicated that air yam flour and the lasagna dough had high dietary fiber contents, 17.1% and 9.4%, respectively. Additionally, the low-fat content found means that the lasagna dough can be considered both gluten-free and fat-free. The most bioaccessible mineral present was K in both air yam flour and lasagna dough. In sensory analysis, the lasagna dough containing air yam showed an intermediate acceptability in relation to two already commercialized lasagna doughs. This study shows an application to this group of plants that are still little explored, allowing the development to consumers and industries.

Solid-State NMR of Membrane Proteins in Lipid Bilayers: To Spin or Not To Spin?

Membrane proteins mediate a plethora of cellular functions and represent important targets for drug development. Unlike soluble proteins, membrane proteins require native-like environments to fold correctly and be active. Therefore, modern structural biology techniques have aimed to determine the structure and dynamics of these membrane proteins at physiological temperature and in liquid crystalline lipid bilayers. With the flourishing of new NMR methodologies and improvements in sample preparations, magic angle spinning (MAS) and oriented sample solid-state NMR (OS-ssNMR) spectroscopy of membrane proteins is experiencing a new renaissance. Born as antagonistic approaches, these techniques nowadays offer complementary information on the structural topology and dynamics of membrane proteins reconstituted in lipid membranes. By spinning biosolid samples at the magic angle (θ = 54.7°), MAS NMR experiments remove the intrinsic anisotropy of the NMR interactions, increasing spectral resolution. Internuclear spin interactions (spin exchange) are reintroduced by RF pulses, providing distances and torsion angles to determine secondary, tertiary, and quaternary structures of membrane proteins. OS-ssNMR, on the other hand, directly detects anisotropic NMR parameters such as dipolar couplings (DC) and anisotropic chemical shifts (CS), providing orientational constraints to determine the architecture (i.e., topology) of membrane proteins relative to the lipid membrane. Defining the orientation of membrane proteins and their interactions with lipid membranes is of paramount importance since lipid-protein interactions can shape membrane protein conformations and ultimately define their functional states.In this Account, we report selected studies from our group integrating MAS and OS-ssNMR techniques to give a comprehensive view of the biological processes occurring at cellular membranes. We focus on the main experiments for both techniques, with an emphasis on new implementation to increase both sensitivity and spectral resolution. We also describe how the structural constraints derived from both isotropic and anisotropic NMR parameters are integrated into dynamic structural modeling using replica-averaged orientational-restrained molecular dynamics simulations (RAOR-MD). We showcase small membrane proteins that are involved in Ca2+ transport and regulate cardiac and skeletal muscle contractility: phospholamban (PLN, 6 kDa), sarcolipin (SLN, 4 kDa), and DWORF (4 kDa). We summarize our results for the structures of these polypeptides free and in complex with the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA, 110 kDa). Additionally, we illustrate the progress toward the determination of the structural topology of a six transmembrane protein associated with succinate and acetate transport (SatP, hexamer 120 kDa). From these examples, the integrated MAS and OS-ssNMR approach, in combination with modern computational methods, emerges as a way to overcome the challenges posed by studying large membrane protein systems.

PHRONESIS: A One-Shot Approach for Sequential Assignment of Protein Resonances by Ultrafast MAS Solid-State NMR Spectroscopy.

Solid-state NMR (ssNMR) spectroscopy has emerged as the method of choice to analyze the structural dynamics of fibrillar, membrane-bound, and crystalline proteins that are recalcitrant to other structural techniques. Recently, 1 H detection under fast magic angle spinning and multiple acquisition ssNMR techniques have propelled the structural analysis of complex biomacromolecules. However, data acquisition and resonance-specific assignments remain a bottleneck for this technique. Here, we present a comprehensive multi-acquisition experiment (PHRONESIS) that simultaneously generates up to ten 3D 1 H-detected ssNMR spectra. PHRONESIS utilizes broadband transfer and selective pulses to drive multiple independent polarization pathways. High selectivity excitation and de-excitation of specific resonances were achieved by high-fidelity selective pulses that were designed using a combination of an evolutionary algorithm and artificial intelligence. We demonstrated the power of this approach with microcrystalline U-13 C,15 N GB1 protein, reaching 100 % of the resonance assignments using one data set of ten 3D experiments. The strategy outlined in this work opens up new avenues for implementing novel 1 H-detected multi-acquisition ssNMR experiments to speed up and expand the application to larger biomolecular systems.

Probing the Lithium Substructure and Ionic Conductivity of the Solid Electrolyte Li4PS4I.

In search of high-performance solid electrolytes, various materials have been discovered in the past, approaching or even exceeding the ionic conductivity of conventional liquid electrolytes. Among the reported classes of superionic electrolytes for solid-state battery applications, lithium thiophosphates appear to be the most promising owing to their high ionic conductivity and mechanical softness. A recent example is the Li4PS4I phase (P4/nmm). Surprisingly, this material shows a comparatively low ionic conductivity at room temperature ranging from 10-4 to 10-5 S cm-1 despite having favorable structural characteristics. Because of discrepancies between experiment and theory regarding the Li-ion conductivity and polymorphism in Li4PS4I, we herein examine the crystal structure over a broad temperature range using ex situ and in situ X-ray and neutron powder diffraction techniques. We demonstrate the absence of polymorphic transitions, with a lithium redistribution at low temperatures though, and confirm the relatively poor room-temperature ionic conductivity despite the presence of a three-dimensional (3D) percolation network for facile charge transport.

PIK3CA Mutational Analysis in Patients With Macrodactyly.

BACKGROUND: Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future. METHODS: We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient's records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material. RESULTS: Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation. CONCLUSION: Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors.

The impact of on-site cardiac rhythm on mortality in patients supported with extracorporeal cardiopulmonary resuscitation: A retrospective cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used in patients with out-of-hospital or in-hospital cardiac arrest in whom conventional cardiopulmonary resuscitation remains unsuccessful. The aim of this study was to analyze the impact of initial cardiac rhythm-detected on-site of the cardiac arrest-on mortality. METHODS: We performed a retrospective cohort study of patients who received ECPR in our tertiary care cardiac arrest center. Patients were divided into three groups depending on their cardiac rhythm: shockable rhythm, pulseless electrical activity, and asystole. The primary endpoint was mortality within the first 7 days after ECPR deployment. Secondary endpoints were mortality within 28 days and the impact of pre-ECPR potassium, serum lactate, pH, and pCO2 on mortality. The association of the initial cardiac rhythm and the location of arrhythmia detection (patient monitored in hospital [category: monitored], not monitored but hospitalized [in-hospital], not monitored, not hospitalized [out-of hospital]) with the primary and secondary outcome was examined by means of univariable and multivariable logistic regression. RESULTS: Sixty-five patients could be included in the final analysis. Thirty-two patients (49.2%, 95%CI 36.6%-61.9%) died within the first 7 days. In terms of 7-day-mortality patients differed in the initial cardiac rhythm (p = 0.040) and with respect to the location of arrhythmia detection (p = 0.002). Shockable cardiac rhythm (crude OR 0.21; 95%CI 0.03-0.98) and pulseless electrical activity (0.13; 0.02-0.61) as the initial rhythm on-site showed better odds for survival compared to asystole. However, this association did neither persist in adjusted analysis nor pairwise comparison. DISCUSSION: The study could not demonstrate a better outcome with shockable rhythm after ECPR. More homogeneous and adequately powered cohorts are needed to better understand the impact of cardiac rhythm on patient outcomes after ECPR.

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.

BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases. METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Zurich Appearance Score for Hands: Development and Validation of an Instrument for Assessing Hand Appearance in Congenital Upper Limb Differences.

PURPOSE: The appearance of the hand is relevant to individual activity and participation. Improving appearance is often one of the essential goals of hand surgery. The aim of this study was to describe and validate an instrument for quantitatively assessing hand appearance in congenital upper limb differences (CULD). METHODS: The Zurich Appearance Score for Hands (ZASH) was developed as a summed score of 6 items: 1 for overall appearance and 5 specific items for the skin, proportions of the hand, the number of digits, the shape of fingers and the thumb, and the position of the thumb. Each item can be rated on an 11-point Likert scale. Here, 448 participants (age, 14-83 years) were asked to rate the images of 17 hands, including standardized 3-dimensional photorealistic computer graphics and photographs of children's hands with or without CULDs, some after surgical correction. The sociodemographic characteristics of the participants were measured using a short questionnaire. RESULTS: The ZASH score for all CULDs was significantly lower than the ZASH score for normal hands. Correlations for overall appearance and the ZASH score were high (r = 0.77-0.87). The internal consistency of all ZASH scores was good to excellent (Cronbach α = 0.82-0.94). The test-retest reliability in a subgroup of 54 participants was good (r = 0.53-0.79). The interrater reliability of the ZASH score was moderate (intraclass correlation = 0.47). CONCLUSIONS: The ZASH is a valid and moderately reliable instrument for assessing hand appearance in children with CULDs. CLINICAL RELEVANCE: Achieving the best possible appearance is the one of the most relevant goals of hand surgery. Assessment with validated instruments provides evidence on how to approach this goal. Further studies may clarify whether the ZASH can be recommended for all hand conditions and to what extent observers' sociocultural and professional backgrounds affect perception.

PISA-SPARKY: an interactive SPARKY plugin to analyze oriented solid-state NMR spectra of helical membrane proteins.

MOTIVATION: Two-dimensional [15N-1H] separated local field solid-state nuclear magnetic resonance (NMR) experiments of membrane proteins aligned in lipid bilayers provide tilt and rotation angles for α-helical segments using Polar Index Slant Angle (PISA)-wheel models. No integrated software has been made available for data analysis and visualization. RESULTS: We have developed the PISA-SPARKY plugin to seamlessly integrate PISA-wheel modeling into the NMRFAM-SPARKY platform. The plugin performs basic simulations, exhaustive fitting against experimental spectra, error analysis and dipolar and chemical shift wave plotting. The plugin also supports PyMOL integration and handling of parameters that describe variable alignment and dynamic scaling encountered with magnetically aligned media, ensuring optimal fitting and generation of restraints for structure calculation. AVAILABILITY AND IMPLEMENTATION: PISA-SPARKY is freely available in the latest version of NMRFAM-SPARKY from the National Magnetic Resonance Facility at Madison (http://pine.nmrfam.wisc.edu/download_packages.html), the NMRbox Project (https://nmrbox.org) and to subscribers of the SBGrid (https://sbgrid.org). The pisa.py script is available and documented on GitHub (https://github.com/weberdak/pisa.py) along with a tutorial video and sample data. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Gate-tunable spin waves in antiferromagnetic atomic bilayers.

Remarkable properties of two-dimensional (2D) layer magnetic materials, which include spin filtering in magnetic tunnel junctions and the gate control of magnetic states, were demonstrated recently1-12. Whereas these studies focused on static properties, dynamic magnetic properties, such as excitation and control of spin waves, remain elusive. Here we investigate spin-wave dynamics in antiferromagnetic CrI3 bilayers using an ultrafast optical pump/magneto-optical Kerr probe technique. Monolayer WSe2 with a strong excitonic resonance was introduced on CrI3 to enhance the optical excitation of spin waves. We identified subterahertz magnetic resonances under an in-plane magnetic field, from which the anisotropy and interlayer exchange fields were determined. We further showed tuning of the antiferromagnetic resonances by tens of gigahertz through electrostatic gating. Our results shed light on magnetic excitations and spin dynamics in 2D magnetic materials, and demonstrate their potential for applications in ultrafast data storage and processing.

Sensitive Blood-Based Detection of Asbestos-Associated Diseases Using Cysteine-Rich Angiogenic Inducer 61 as Circulating Protein Biomarker.

BACKGROUND: Detection of asbestos-associated diseases like asbestosis or mesothelioma is still challenging. We sought to improve the diagnosis of benign asbestos-associated disease (BAAD) by detection of the protein cysteine-rich angiogenic inducer 61 (Cyr61) in human plasma. METHODS: Plasma Cyr61 was quantified using an enzyme-linked immunosorbent assay. Plasma samples from males diagnosed with BAAD, but without a malignant disease (n = 101), and malignant mesothelioma (n = 21; 15 males, 6 females), as well as nonasbestos-exposed healthy control participants (n = 150; 58 males, 92 females) were analyzed. Clinical sensitivity and specificity of Cyr61 were determined by receiver operating characteristic analysis. RESULTS: The median plasma Cyr61 concentration for healthy control participants was 0.27 ng/mL. Cytoplasmic Cyr61 in peripheral blood mononuclear cells from healthy control participants was evenly distributed, as detected by immunofluorescent staining. The increase in plasma Cyr61 concentrations in the BAAD study group was statistically significant compared to the healthy control participants (P < 0.0001). For the detection of BAAD vs male healthy control participants, clinical sensitivity was 88% and clinical specificity 95% with an area under the curve of 0.924 at maximal Youden Index. For a predefined clinical specificity of 100%, the clinical sensitivity was 76%. For male mesothelioma patients vs male healthy control participants, the clinical sensitivity at maximal Youden Index was 95% with a clinical specificity of 100% (area under the curve, 0.997) and for a predefined clinical specificity of 100%, the clinical sensitivity was 93%. CONCLUSIONS: In our study, plasma Cyr61 protein concentrations showed to be a new biomarker for asbestos-associated diseases like BAAD and mesothelioma in men, which deserves further investigation in large-scale cohort studies.

Strategic Considerations for Applying the Flipped Classroom to Neurology Education.

Nowadays, the "flipped classroom" approach is taking the center stage within medical education. However, very few reports on the implementation of the flipped classroom in neurology have been published to date, and this educational model still represents a challenge for students and educators alike. In this article, neurology educators from the American Academy of Neurology's A. B. Baker Section on Neurological Education analyze reports of flipped classroom in other medical/surgical subspecialties, review the current implementation in neurology, and discuss future strategies to flip the neurology curriculum through contextualization of the benefits and the consequences. ANN NEUROL 2020;87:4-9.

Expression and purification of the native C-amidated antimicrobial peptide maculatin 1.1.

Maculatin 1.1 (Mac1) is an antimicrobial peptide (AMP) from an Australian tree frog and exhibits low micromolar activity against Gram-positive bacteria. The antimicrobial properties of Mac1 are linked to its disruption of bacterial lipid membranes, which has been studied extensively by in vitro nuclear magnetic resonance (NMR) spectroscopy and biophysical approaches. Although in vivo NMR has recently proven effective in probing peptide-lipid interplay in live bacterial cells, direct structural characterisation of AMPs has been prohibited by low sensitivity and overwhelming background noise. To overcome this issue, we report a recombinant expression protocol to produce isotopically enriched Mac1. We utilized a double-fusion construct to alleviate toxicity against the Escherichia coli host and generate the native N-free and C-amidated termini Mac1 peptide. The SUMO and intein tags allowed native N-terminus and C-terminal amidation, respectively, to be achieved in a one-pot reaction. The protocol yielded 0.1 mg/L of native, uniformly 15 N-labelled, Mac1, which possessed identical structure and activity to peptide obtained by solid-phase peptide synthesis.