A study on interoperability between two Personal Health Train infrastructures in leukodystrophy data analysis.

The development of platforms for distributed analytics has been driven by a growing need to comply with various governance-related or legal constraints. Among these platforms, the so-called Personal Health Train (PHT) is one representative that has emerged over the recent years. However, in projects that require data from sites featuring different PHT infrastructures, institutions are facing challenges emerging from the combination of multiple PHT ecosystems, including data governance, regulatory compliance, or the modification of existing workflows. In these scenarios, the interoperability of the platforms is preferable. In this work, we introduce a conceptual framework for the technical interoperability of the PHT covering five essential requirements: Data integration, unified station identifiers, mutual metadata, aligned security protocols, and business logic. We evaluated our concept in a feasibility study that involves two distinct PHT infrastructures: PHT-meDIC and PADME. We analyzed data on leukodystrophy from patients in the University Hospitals of Tübingen and Leipzig, and patients with differential diagnoses at the University Hospital Aachen. The results of our study demonstrate the technical interoperability between these two PHT infrastructures, allowing researchers to perform analyses across the participating institutions. Our method is more space-efficient compared to the multi-homing strategy, and it shows only a minimal time overhead.

[Change in the age spectrum in strabismus surgery]. / Änderung des Altersspektrums in der Strabismus-Chirurgie.

BACKGROUND: The proportion of children undergoing strabismus surgery in the total volume of eye muscle operations appears to have decreased. To verify this we analyzed the age of patients who underwent extraocular muscle (EOM) surgery. METHODS: The data of patients who underwent EOM surgery at the University Eye Hospital Giessen between 1991 and 2019 were reviewed and the numbers of operations in decadal age groups were compared to the German population in the respective period. In addition, the types of strabismus which led to surgery were evaluated. The data pool comprised > 25,000 surgeries involving > 60,000 muscles. RESULTS: In comparison to 1991, in 2019 the proportion of children aged ≤ 10 years decreased from 50.2% to 31.8%, corresponding to a relative decrease of more than one third. The proportion of patients aged > 50 years increased from 6.5% to 22.5%, i.e., by a factor > 3, while the population ≤ 10 years in 2019 was 13% smaller than in 1991 and the population aged > 50 years increased by 37%. The major reason for the decreasing proportion of children was a 53% reduction in surgery for esotropia. We found no apparent changes in the 2nd-5th decades of life. DISCUSSION AND CONCLUSION: The lower proportion of children undergoing EOM surgery appears to indicate an improvement in vision screening during the past 4 decades. The increasing proportion of older patients may result from better information on potential treatment and increased incidence of acquired strabismus with corresponding complaints. The demographic shift played a secondary role. Due to the population structure in Germany, a further increase in the demand for EOM surgery is to be expected.

The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition.

Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent.

[High-dose medialis recession in latent nystagmus]. / Hoch dosierte Medialisrücklagerung bei Nystagmus vom Latenstyp.

BACKGROUND: Large muscle recessions reduce anomalous head turn (AHT) in infantile nystagmus syndrome (INS). Their quantitative effect to reduce AHT in fusion maldevelopment nystagmus syndrome (FMNS) is unknown. AIM OF THE STUDY: To evaluate the reduction of AHT by large medial rectus muscle recession in patients with FMNS. METHODS: We analyzed data of 12 patients with pure FMNS who received large medial rectus muscle recessions on the sound eye or only eye between 2014 and 2019. Medians and ranges (min-max) were: age at surgery 14 years (3-43 years); decimal BCVA sound eye/fellow eye 0.56 (0.4-1.0)/0.01 (0-0.4); AHT at 5 m/0.3 m fixation distance 35° (15-45°)/20° (0-45°); amount of recession 13 mm (11.5-15 mm); follow-up 13 (4-39) months. RESULTS: At the final visit, AHT at 5 m/0.3 m was 10° (0-20°/0-15°). The individual reduction of AHT at 5 m amounted to 25° (8-35°) without any overcorrection. The available visual field of functionally monocular patients increased correspondingly. Slight overcorrection at 0.3 m occurred in 2 cases. Adduction of the sound eye was limited to 25e-40°). BCVA and anomalous head posture in vertical and frontal planes did not improve. CONCLUSION: Large medial rectus muscle recession on the sound eye improves AHT in FMNS by a similar amount compared to INS and the available visual field of functionally monocular patients.

Radio-Frequency Manipulation of State Populations in an Entangled Fluorine-Muon-Fluorine System.

Entangled spin states are created by implanting muons into single-crystal LiY_{0.95}Ho_{0.05}F_{4} to form a cluster of correlated, dipole-coupled local magnetic moments. The resulting states have well-defined energy levels allowing experimental manipulation of the state populations by electromagnetic excitation. Experimental control of the evolution of the muon spin polarization is demonstrated through application of continuous, radio-frequency electromagnetic excitation fields. A semiclassical model of quantum, dipole-coupled spins interacting with a classical, oscillating magnetic field accounts for the muon spin evolution. On application of the excitation field, this model shows how changes in the state populations lead to the experimentally observed effects, thus enabling a spectroscopic probe of entangled spin states with muons.

Application of leaf analysis in addition to growth assessment to evaluate the suitability of greywater for irrigation of Tilia cordata and Acer pseudoplatanus.

Water is the key resource in fulfilling the cooling function of plants in urban environments and needs to be supplied reliably and adequately, especially during dry periods. To avoid an unsustainable use of high-quality drinking water for irrigation, the reuse of greywater should be implemented for Green Infrastructure irrigation in the sense of the circular economy. In this study, the influence of greywater irrigation on vitality of two trees species, Tilia cordata and Acer pseudoplatanus, was determined by investigating the effect of irrigation with raw or treated greywater in comparison to municipal tap water. Plant growth parameters were measured, including leaf area, number of leaves, average leaf area and annual growth. In addition, the relative chlorophyll content was determined and image analysis was used to identify vital and necrotic leaf parts. While treatment did not affect growth after one growing season A. pseudoplatanus had significantly higher leaf necrosis (34.8%) when irrigated with raw greywater compared to treated greywater (15.5%) and tap water (5.8%). Relative chlorophyll content of T. cordata irrigated with tap water decreased over time until it was significantly lower (28.5) then the greywater treatments (34.5 and 35). Image analysis of leaves to quantify necrosis proved to be a sensitive method to quantify plant health and showed negative effects earlier than an analysis of growth. Anionic surfactants and electrical conductivity had a significant influence on plant vitality. Therefore, plant selection should take these parameters into account, when planning green infrastructure irrigated with greywater.

First demonstration of tuning between the Kitaev and Ising limits in a honeycomb lattice.

Recent observations of novel spin-orbit coupled states have generated interest in 4d/5d transition metal systems. A prime example is the [Formula: see text] state in iridate materials and α-RuCl3 that drives Kitaev interactions. Here, by tuning the competition between spin-orbit interaction (λSOC) and trigonal crystal field (ΔT), we restructure the spin-orbital wave functions into a previously unobserved [Formula: see text] state that drives Ising interactions. This is done via a topochemical reaction that converts Li2RhO3 to Ag3LiRh2O6. Using perturbation theory, we present an explicit expression for the [Formula: see text] state in the limit ΔT ≫ λSOC realized in Ag3LiRh2O6, different from the conventional [Formula: see text] state in the limit λSOC ≫ ΔT realized in Li2RhO3. The change of ground state is followed by a marked change of magnetism from a 6 K spin-glass in Li2RhO3 to a 94 K antiferromagnet in Ag3LiRh2O6.

High-Frequency ac Susceptibility of Iron-Based Superconductors.

A microwave technique suitable for investigating the AC magnetic susceptibility of small samples in the GHz frequency range is presented. The method-which is based on the use of a coplanar waveguide resonator, within the resonator perturbation approach-allows one to obtain the absolute value of the complex susceptibility, from which the penetration depth and the superfluid density can be determined. We report on the characterization of several iron-based superconducting systems, belonging to the 11, 122, 1144, and 12442 families. In particular, we show the effect of different kinds of doping for the 122 family, and the effect of proton irradiation in a 122 compound. Finally, the paradigmatic case of the magnetic superconductor EuP-122 is discussed, since it shows the emergence of both superconducting and ferromagnetic transitions, marked by clear features in both the real and imaginary parts of the AC susceptibility.

[Three-muscle surgery for large angle esotropia]. / Dreimuskelchirurgie bei großwinkliger Esotropie.

BACKGROUND: Bilateral medial rectus muscle recession with or without Cüppers' posterior fixation suture and recess and resect surgery are used to correct for large angle esotropia. There are only few reports on three muscle surgery (3MS). We analyzed the results of 3MS. PATIENTS AND METHODS: Between June 2016 and May 2020, 61 patients received 3MS for esotropia ≥ 27° (50 PD) together with oblique muscle surgery, if needed. Angles of strabismus were measured by simultaneous prism and cover testing (SPCT) and alternating prism and cover testing (APCT) at 5 m and 0.3 m. Grading was around 0.51 mm/degree (at 5 m). Medium-term results of 57 patients were available. RESULTS: Medians and ranges (min-max) were: age, 6 years (3-56 years). Preoperative APCT, far 34° (27-45°), near 36° (27-50°). Amount of surgery, 17 mm (15-21 mm), oblique muscle recession in 21 cases. The APCT after 5 months (3-24 months), far 2° (-10-18), near 2° (-8-18). Success rates (absolute deviation ≤ 6° [10 PD]), APCT far 68%, near 67%, SPCT far 79%, near 74%. Exotropia > 6° occurred in 4 cases (7%) at far and 3 (5%) at near, esotropia > 6° in 14 cases (25%) at far and 16 (28%) at near. CONCLUSION: The use of 3MS is a suitable first step procedure to correct for large angle esotropia.

Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics.

Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.

[Bridle operation for incomplete oculomotor nerve paralysis (superior rectus and lateral rectus nasal inferior transposition)]. / Die Zügeloperation bei inkompletter Okulomotoriusparalyse (Rectus-superior- und Rectus-lateralis-Transposition nach nasal unten).

PURPOSE: To demonstrate the technique and effectiveness of the bridle operation for oculomotor nerve paralysis with maintained elevation. METHOD: The bridle operation includes transposition of the lateral rectus muscle (passing behind inferior oblique and rectus muscles) and the superior rectus muscle (behind superior oblique tendon and medial rectus muscle) to the nasal inferior surface of the globe. RESULTS: In the reported case, this procedure corrected exo-hypertropia of 30-40°/20-30° without inducing cyclotropia. CONCLUSION: The bridle operation expands the surgical arsenal for paralytic strabismus.

Yokoyama procedure for esotropia associated with high myopia: real-world data from a large-scale multicentre analysis.

PURPOSE: High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far. METHODS: We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models. RESULTS: We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia. CONCLUSION: Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large-scale real-world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.

Absence of local moments in the kagome metal KV3Sb5as determined by muon spin spectroscopy.

We have carried out muon spin relaxation and rotation measurements on the newly discovered kagome metal KV3Sb5, and find a local field dominated by weak magnetic disorder which we associate with the nuclear moments present, and a modest temperature dependence which tracks the bulk magnetic susceptibility. We find no evidence for the existence of V4+local moments, suggesting that the physics underlying the recently reported giant unconventional anomalous Hall effect in this material warrants further studies.

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.

Microscopic Detection Analysis of Single Molecules in MoS2 Membrane Nanopores.

A systematic microscopic analysis of the various resistive effects involved in the electronic detection of single biomolecules in a nanopore of a MoS2 nanoribbon is presented. The variations of the transverse electronic current along the two-dimensional (2D) membrane due to the translocation of DNA and protein molecules through the pore are obtained by model calculations based on molecular dynamics (MD) and Boltzmann transport formalism, which achieved good agreement with the experimental data. Our analysis points to a self-consistent interaction among ions, charge carriers around the pore rim, and biomolecules. It provides a comprehensive understanding of the effects of the electrolyte concentration, pore size, nanoribbon geometry, and also the doping polarity of the nanoribbon on the electrical sensitivity of the nanopore in detecting biomolecules. These results can be utilized for fine-tuning the design parameters in the fabrication of highly sensitive 2D nanopore biosensors.

Bifunctional Nitrone-Conjugated Secondary Metabolite Targeting the Ribosome.

Many microorganisms possess the capacity for producing multiple antibiotic secondary metabolites. In a few notable cases, combinations of secondary metabolites produced by the same organism are used in important combination therapies for treatment of drug-resistant bacterial infections. However, examples of conjoined roles of bioactive metabolites produced by the same organism remain uncommon. During our genetic functional analysis of oxidase-encoding genes in the everninomicin producer Micromonospora carbonacea var. aurantiaca, we discovered previously uncharacterized antibiotics everninomicin N and O, comprised of an everninomicin fragment conjugated to the macrolide rosamicin via a rare nitrone moiety. These metabolites were determined to be hydrolysis products of everninomicin P, a nitrone-linked conjugate likely the result of nonenzymatic condensation of the rosamicin aldehyde and the octasaccharide everninomicin F, possessing a hydroxylamino sugar moiety. Rosamicin binds the erythromycin macrolide binding site approximately 60 Å from the orthosomycin binding site of everninomicins. However, while individual ribosomal binding sites for each functional half of everninomicin P are too distant for bidentate binding, ligand displacement studies demonstrated that everninomicin P competes with rosamicin for ribosomal binding. Chemical protection studies and structural analysis of everninomicin P revealed that everninomicin P occupies both the macrolide- and orthosomycin-binding sites on the 70S ribosome. Moreover, resistance mutations within each binding site were overcome by the inhibition of the opposite functional antibiotic moiety binding site. These data together demonstrate a strategy for coupling orthogonal antibiotic pharmacophores, a surprising tolerance for substantial covalent modification of each antibiotic, and a potential beneficial strategy to combat antibiotic resistance.

[Highly dosed Anderson and Kestenbaum operations for anomalous head posture due to nystagmus]. / Hoch dosierte Anderson- und Kestenbaum-Operation bei Nystagmus mit Kopfzwangshaltung.

BACKGROUND: The correction of anomalous head posture associated with infantile nystagmus syndrome (INS) is carried out by the Kestenbaum procedure (KP) combining bilateral horizontal yoke muscle recession with resection of their antagonists or by the Anderson procedure (AP) which is confined to yoke muscle recession alone. AIM OF THE STUDY: To compare the results of highly dosed AP and KP for anomalous head turn (HT). PATIENTS AND METHODS: The AP (2013-2019) and KP (2003-2013) were used as the exclusive procedures during the respective time periods. A highly dosed AP was performed in a case series of 33 consecutive orthotropic patients with INS and KP in 19 orthotropic patients with INS. Medians and ranges (min-max) in groups AP/KP were: age at surgery 7 years (4-44 years)/6 years (4-27 years), HT 32.5° (20-45°)/30° (17-40°) and surgery on each eye AP 13 mm (10-16 mm) (standard dose), KP 10 mm (6-12 mm) + 10 mm (6-12 mm) (mean 0.6 mm/°HT). RESULTS: The HT was diminished to 10° (-3-20°)/10° (-7-20°) ca. 3 months after surgery. At the late visit (8-153 months), the residual HT was 10° (0-20°)/10° (-27-30°). The HT was reduced by 67% (20-100%)/64% (14-100%) at the last control. A residual HT ≤15° was present in 79%/81% of cases (91% after AP ≥13 mm; n = 23) and HT ≤10° in 55%/57%, (65% after AP ≥13 mm). The maximum adduction/abduction towards the recessed muscles was 30°/30° (10-37°/15-45°) after AP and 32°/30° (10-40°/12-45°) after KP. An associated head tilt was not improved by the intervention. Mean binocular visual acuity increased by <1 line in both procedures. After AP the mean increase was 1 line in children ≤6 years old and there was no increase in patients >6 years of age. CONCLUSION: The effectiveness and success rates of AP and KP were similar with the dosing used. Less invasive surgery is an advantage in favor of AP as the primary procedure.