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This White Paper presents an overview of the current status and future perspective of QCD research, based on the community inputs and scientific conclusions from the 2022 Hot and Cold QCD Town Meeting. We present the progress made in the last decade toward a deep understanding of both the fundamental structure of the sub-atomic matter of nucleon and nucleus in cold QCD, and the hot QCD matter in heavy ion collisions. We identify key questions of QCD research and plausible paths to obtaining answers to those questions in the near future, hence defining priorities of our research over the coming decades.

Abstract Background Sustainable agriculture increasingly emphasizes the importance of microbial communities in influencing plant health and productivity. In viticulture, understanding the impact of management practices on fungal communities is critical, given their role in disease dynamics, grape and wine quality. This study investigates the effects of integrated, organic, and biodynamic management practices on the diversity and function of fungal communities in a vineyard located in Geisenheim, Germany, focusing on above-ground parts such as bark, leaves, and grapes. Results Our findings indicate that while overall fungal species richness did not significantly differ among management systems across various compartments, the composition of these communities was distinctly influenced by the type of management system. In particular, leaf and grape compartments showed notable variations in fungal community structure between integrated and organic/biodynamic management. No differences were observed between organic and biodynamic management. Integrated management demonstrated a significantly higher abundance of mycoparasites in comparison to organic and biodynamic management, primarily attributed to the increased presence of Sporobolomyces roseus, Sporobolomyces ellipsoideus and Rhodotorula glutinis. Conclusions The findings highlight the importance of management practices in shaping fungal community composition and function in vineyards. Although overall species richness remained unaffected, community composition and functional diversity varied, highlighting the potential for strategic microbiome management to enhance vineyard sustainability and plant health.

Abstract In certain kinematic and particle mass configurations, triangle singularities may lead to line-shapes which mimic the effects of resonances. This well-known effect is scrutinized here in the presence of final-state rescattering. The goal is achieved first by utilizing general arguments provided by Landau equations, and second by applying a modern scattering formalism with explicit two- and three-body unitarity.

Abstract This paper introduces three novel approaches to size geothermal energy piles in a MILP, offering fresh perspectives and potential solutions. The research overlooks MILP models that incorporate the sizing of a geothermal borefield. Therefore, this paper presents a new model utilizing a g-function model to regulate the power limits. Geothermal energy is an essential renewable source, particularly for heating and cooling. Complex energy systems, with their diverse sources of heating and cooling and intricate interactions, are crucial for a climate-neutral energy system. This work significantly contributes to the integration of geothermal energy as a vital energy source into the modelling of such complex systems. Borehole heat exchangers help generate heat in low-temperature energy systems. However, optimizing these exchangers using mixed-integer-linear programming (MILP), which only allows for linear equations, is complex. The current research only uses R-C, reservoir, or g-function models for pre-sized borefields. As a result, borehole heat exchangers are often represented by linear factors such as 50 W/m for extraction or injection limits. A breakthrough in the accuracy of borehole heat exchanger sizing has been achieved with the development of a new model, which has been rigorously compared to two simpler models. The geothermal system was configured for three energy systems with varying ground and bore field parameters. The results were then compared with existing geothermal system tools. The new model provides more accurate depth sizing with an error of less than 5 % compared to simpler models with an error higher than 50 %, although it requires more calculation time. The new model can lead to more accurate borefield sizing in MILP applications to optimize energy systems. This new model is especially beneficial for large-scale projects that are highly dependent on borefield size.

Abstract There is growing interest in intercropping as a practice to increase productivity per unit area and ecosystem functioning in agricultural systems. Relay intercropping with soy and winter wheat may benefit soil health due to increased diversity and longer undisturbed soil cover, yet this remains largely unstudied. Using a field experiment in Eastern Germany, we studied the temporal dynamics of chemical, biological, and physical indicators of soil health in the topsoil over a year of cultivation to detect early effects of soy-wheat relay intercropping compared to sole cropping. Indicators included microbial abundance, permanganate-oxidizable carbon, carbon fractions, pH, and water infiltration. Relay intercropping showed no unique soil health benefits compared to sole cropping, likely affected by drought that stressed intercropped soy. Relay intercropping did, however, maintain several properties of both sole crops including an increased MAOM C:N ratio and higher soil water infiltration. The MAOM C:N ratio increased by 4.2 and 6.2% in intercropping and sole soy and decreased by 5% in sole wheat. Average near-saturated soil water infiltration rates were 12.6, 14.9, and 6.0 cm hr−1 for intercropping, sole wheat, and sole soy, respectively. Cropping system did not consistently affect other indicators but we found temporal patterns of these indicators, showing their sensitivity to external changes.

The structures of seven gold(III) halide derivatives of general formula LAuX3 (L = methylpyridines or dimethylpyridines, X = Cl or Br) are presented: trichlorido(2-methylpyridine)gold(III), [AuCl3(C6H7N)], 1 (as two polymorphs 1a and 1b); tribromido(2-methylpyridine)gold(III), [AuBr3(C6H7N)], 2; tribromido(3-methylpyridine)gold(III), [AuBr3(C6H7N)], 3; tribromido(2,4-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 4; trichlorido(3,5-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 5; tribromido(3,5-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 6, and trichlorido(2,6-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 7. Additionally, the structure of 8, the 1:1 adduct of 2 and 6, [AuBr3(C6H7N)]·[AuBr3(C7H9N)], is included. All the structures crystallize solvent-free, and all have Z′ = 1 except for 5 and 7, which display crystallographic twofold rotation symmetry, and 4, which has Z′ = 2. 1a and 2 are isotypic. The coordination geometry at the gold(III) atoms is, as expected, square-planar. Four of the crystals (1a, 1b, 2 and 8) were non-merohedral twins, and these structures were refined using the ‘HKLF 5’ method. The largest interplanar angles between the pyridine ring and the coordination plane are observed for those structures with a 2-methyl substituent of the pyridine ring. The Au—N bonds are consistently longer trans to Br (average 2.059 Å) than trans to Cl (average 2.036 Å). In the crystal packing, a frequent feature is the offset-stacked and approximately rectangular dimeric moiety (Au—X)2, with antiparallel Au—X bonds linked by Au...X contacts at the vacant positions axial to the coordination plane. The dimers are connected by further secondary interactions (Au...X or X...X contacts, `weak' C—H...X hydrogen bonds) to form chain, double chain (`ladder') or layer structures, and in several cases linked again in the third dimension. Only 1b and 7 contain no offset dimers; these structures instead involve C—H...Cl hydrogen bonds combined with Cl...Cl contacts (1b) or Cl...π contacts (7). The packing patterns of seven further complexes LAuX3 involving simple pyridines (taken from the Cambridge Structural Database) are compared with those of 1–8.

Abstract Background Propionate is a food preservative and platform chemical, but no biological process competes with current petrochemical production routes yet. Although propionate production has been described for gut bacteria of the class Bacteroidia, which also carry great capacity for the degradation of plant polymers, knowledge on propionate yields and productivities across species is scarce. This study aims to compare propionate production from glucose within Bacteroidia and characterize good propionate producers among this group. Results We collected published information on propionate producing Bacteroidia, and selected ten species to be further examined. These species were grown under defined conditions to compare their product formation. While propionate, acetate, succinate, lactate and formate were produced, the product ratios varied greatly among the species. The two species with highest propionate yield, B. propionicifaciens (0.39 gpro/ggluc) and B. graminisolvens (0.25 gpro/ggluc), were further examined. Product formation and growth behavior differed significantly during CO2-limited growth and in resting cells experiments, as only B. graminisolvens depended on external-added NaHCO3, while their genome sequences only revealed few differences in the major catabolic pathways. Carbon mass and electron balances in experiments with resting cells were closed under the assumption that the oxidative pentose pathway was utilized for glucose oxidation next to glycolysis in B. graminisolvens. Finally, during pH-controlled fed-batch cultivation B. propionicifaciens and B. graminisolvens grew up to cell densities (OD600) of 8.1 and 9.8, and produced 119 mM and 33 mM of propionate from 130 and 105 mM glucose, respectively. A significant production of other acids, particularly lactate (25 mM), was observed in B. graminisolvens only. Conclusions We obtained the first broad overview and comparison of propionate production in Bacteroidia strains. A closer look at two species with comparably high propionate yields, showed significant differences in their physiology. Further studies may reveal the molecular basis for high propionate yields in Bacteroidia, paving the road towards their biotechnological application for conversion of biomass-derived sugars to propionate.

Bis(2-methylpyridine)gold(I) dibromidoaurate(I), [Au(C6H7N)2][AuBr2], (1), crystallizes in space group C2/c with Z = 4. Both gold atoms lie on twofold axes and are connected by an aurophilic contact. A second aurophilic contact leads to infinite chains of alternating cations and anions parallel to the b axis, and the residues are further connected by a short H...Au contact and a borderline Br...Br contact. Bis(3-methylpyridine)gold(I) dibromidoaurate(I), [Au(C6H7N)2][AuBr2], (2), crystallizes in space group C2/m with Z = 2. Both gold atoms lie on special positions with symmetry 2/m and are connected by an aurophilic contact; all other atoms except for one methyl hydrogen lie in mirror planes. The extended structure is closely analogous to that of 1, although the structures are formally not isotypic. Bis(3,5-dimethylpyridine)gold(I) dichloridoaurate(I), [Au(C7H9N)2][AuCl2], (3) crystallizes in space group P\overline{1} with Z = 2. The cation lies on a general position, and there are two independent anions in which the gold atoms lie on inversion centres. The cation and one anion associate via three short H...Cl contacts to form a ribbon structure parallel to the b axis; aurophilic contacts link adjacent ribbons. Bis(3,5-dimethylpyridine)gold(I) dibromidoaurate(I), [Au(C7H9N)2][AuBr2], (4) is isotypic to 3. Attempts to make similar compounds involving 2-bromopyridine led instead to 2-bromopyridinium dibromidoaurate(I)–2-bromopyridine (1/1), (C5H5BrN)[AuBr2]·C5H4BrN, (5), which crystallizes in space group P\overline{1} with Z = 2; all atoms lie on general positions. The 2-bromopyridinium cation is linked to the 2-bromopyridine molecule by an N—H...N hydrogen bond. Two formula units aggregate to form inversion-symmetric dimers involving Br...Br, Au...Br and H...Br contacts.

Abstract Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay for blood samples from recently diagnosed motor Parkinson’s patients (n = 99), pre-motor individuals with isolated REM sleep behaviour disorder (two cohorts: n = 18 and n = 54 longitudinally), and healthy controls (n = 36). Our machine-learning model accurately identifies all Parkinson patients and classifies 79% of the pre-motor individuals up to 7 years before motor onset by analysing the expression of eight proteins—Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, and Plasma-protease-C1-inhibitor. Many of these biomarkers correlate with symptom severity. This specific blood panel indicates molecular events in early stages and could help identify at-risk participants for clinical trials aimed at slowing/preventing motor Parkinson’s disease.

Abstract Background Image-based crop growth modeling can substantially contribute to precision agriculture by revealing spatial crop development over time, which allows an early and location-specific estimation of relevant future plant traits, such as leaf area or biomass. A prerequisite for realistic and sharp crop image generation is the integration of multiple growth-influencing conditions in a model, such as an image of an initial growth stage, the associated growth time, and further information about the field treatment. While image-based models provide more flexibility for crop growth modeling than process-based models, there is still a significant research gap in the comprehensive integration of various growth-influencing conditions. Further exploration and investigation are needed to address this gap. Methods We present a two-stage framework consisting first of an image generation model and second of a growth estimation model, independently trained. The image generation model is a conditional Wasserstein generative adversarial network (CWGAN). In the generator of this model, conditional batch normalization (CBN) is used to integrate conditions of different types along with the input image. This allows the model to generate time-varying artificial images dependent on multiple influencing factors. These images are used by the second part of the framework for plant phenotyping by deriving plant-specific traits and comparing them with those of non-artificial (real) reference images. In addition, image quality is evaluated using multi-scale structural similarity (MS-SSIM), learned perceptual image patch similarity (LPIPS), and Fréchet inception distance (FID). During inference, the framework allows image generation for any combination of conditions used in training; we call this generation data-driven crop growth simulation. Results Experiments are performed on three datasets of different complexity. These datasets include the laboratory plant Arabidopsis thaliana (Arabidopsis) and crops grown under real field conditions, namely cauliflower (GrowliFlower) and crop mixtures consisting of faba bean and spring wheat (MixedCrop). In all cases, the framework allows realistic, sharp image generations with a slight loss of quality from short-term to long-term predictions. For MixedCrop grown under varying treatments (different cultivars, sowing densities), the results show that adding these treatment information increases the generation quality and phenotyping accuracy measured by the estimated biomass. Simulations of varying growth-influencing conditions performed with the trained framework provide valuable insights into how such factors relate to crop appearances, which is particularly useful in complex, less explored crop mixture systems. Further results show that adding process-based simulated biomass as a condition increases the accuracy of the derived phenotypic traits from the predicted images. This demonstrates the potential of our framework to serve as an interface between a data-driven and a process-based crop growth model. Conclusion The realistic generation and simulation of future plant appearances is adequately feasible by multi-conditional CWGAN. The presented framework complements process-based models and overcomes their limitations, such as the reliance on assumptions and the low exact field-localization specificity, by realistic visualizations of the spatial crop development that directly lead to a high explainability of the model predictions.

Schools serve as social institutions that convey values in the context of socialization and enculturation. Teachers are pivotal in this transmission process via their value-related educational goals (VrEGs), which outline how they would like to see their pupils in terms of values. What factors influence these VrEGs? We suggest that those vary on an individual level, but also correspond to the prevailing value orientations of the society. In our study we followed two main goals to test this thesis. Firstly, we examine the differences in VrEGs between teachers of two European countries: Switzerland (CH) and United Kingdom (UK). Secondly, we investigated the similarity of the teachers’ VrEGs with prevailing national value orientations from the specific countries. One hundred and fifty primary school teachers (108 CH, 42 UK) were asked about their VrEGs using an adapted version of Schwartz’s Portrait Values Questionnaire (PVQ-21). Data from the Human Value Scale (HVS) of the European Social Survey (ESS) was used for country-specific value orientations. Analyses of the value structures and the differences in value priorities showed that for the individuals from the two countries as well as for the teachers’ VrEGs from the two countries, significant differences exist in several value types. Teachers’ VrEGs in each country showed a high correlation with the corresponding national value profile. We discuss our results in light of cross-national differences in value education in schools.

Type 2 innate lymphoid cells (ILC2s) have emerged as pivotal regulators in the pathogenesis of diseases, with their roles in inflammation, metabolism, and tissue homeostasis becoming increasingly recognized. This review provides an overview of the current understanding of ILC2s in inflammation and metabolic disorders, including their functional contributions. Moreover, we will discuss how these cells adapt their metabolic processes to support their function and survival and how their metabolic requirements change under different physiological and pathological conditions. Lastly, we will review recent omics studies that have provided insights into the molecular and cellular characteristics of ILC2s. This includes transcriptomic, proteomic, and metabolomic analyses that have elucidated the gene expression profiles, protein interactions, and metabolic networks, respectively, associated with ILC2s. These studies have advanced our understanding of the functional diversity of ILC2s and their involvement in metabolic disease.

Here we present the generation of HIMRi006-A and HIMRi007-A Pompe disease (PD) patient derived human induced pluripotent stem cell (hiPSC) lines. HIMRi006-A represents an infantile onset disease (IOPD) phenotype caused by a homozygous c.307 T > G mutation in the GAA gene. HIMRi007-A is characterized by heterozygous mutations c.–32–13 T > G/c.1716C > G and is associated with an adult onset of disease symptoms (LOPD). Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4, and c-MYC. The lines display a typical embryonic stem cell morphology, express pluripotency markers, retain a normal karyotype (46, XX/XY) and have the differentiation capacity in all three germ layers. Altogether, both lines provide a resource tool to the community for future in depth molecular studies of PD pathomechanism.

This White Paper presents the community inputs and scientific conclusionsfrom the Hot and Cold QCD Town Meeting that took place September 23-25, 2022 atMIT, as part of the Nuclear Science Advisory Committee (NSAC) 2023 Long RangePlanning process. A total of 424 physicists registered for the meeting. Themeeting highlighted progress in Quantum Chromodynamics (QCD) nuclear physicssince the 2015 LRP (LRP15) and identified key questions and plausible paths toobtaining answers to those questions, defining priorities for our research overthe coming decade. In defining the priority of outstanding physicsopportunities for the future, both prospects for the short (~ 5 years) andlonger term (5-10 years and beyond) are identified together with thefacilities, personnel and other resources needed to maximize the discoverypotential and maintain United States leadership in QCD physics worldwide. ThisWhite Paper is organized as follows: In the Executive Summary, we detail theRecommendations and Initiatives that were presented and discussed at the TownMeeting, and their supporting rationales. Section 2 highlights major progressand accomplishments of the past seven years. It is followed, in Section 3, byan overview of the physics opportunities for the immediate future, and inrelation with the next QCD frontier: the EIC. Section 4 provides an overview ofthe physics motivations and goals associated with the EIC. Section 5 is devotedto the workforce development and support of diversity, equity and inclusion.This is followed by a dedicated section on computing in Section 6. Section 7describes the national need for nuclear data science and the relevance to QCDresearch.

Abstract Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration and potentially relevant as biomarkers, but data on early Parkinson’s disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy and synaptic function in cerebrospinal fluid (CSF) of drug-naïve de novo PD, and sex-/age-matched healthy controls (HC) cross-sectionally (88 PD, 46 HC) and longitudinally (104 PD, 58 HC) over 10 years. Multiple markers of autophagy, synaptic plasticity, and secretory pathways were reduced in PD. We added samples from prodromal subjects (9 cross-sectional, 12 longitudinal) with isolated REM sleep behavior disorder, revealing secretogranin-2 already decreased compared to controls. Machine learning identified neuronal pentraxin receptor and neurosecretory protein VGF as most relevant for discriminating between groups. CSF levels of LAMP2, neuronal pentraxins, and syntaxins in PD correlated with clinical progression, showing predictive potential for motor- and non-motor symptoms as a valid basis for future drug trials.

Trichlorido(4-methylpiperidine)gold(III), [AuCl3(C6H13N)], 1, crystallizes in Pbca with Z = 8. Tribromido(4-methylpiperidine)gold(III), [AuBr3(C6H13N)], 2, crystallizes as two polymorphs, 2a in Pnma with Z = 4 (imposed mirror symmetry) and 2b, which is isotypic to 1. The Au—N bonds trans to Cl are somewhat shorter than those trans to Br, and the Au—Cl bonds trans to N are longer than those cis to N, whereas the Au—Br bonds trans to N are slightly shorter than the cis bonds. The methyl and AuX3 groups (X = halogen) occupy equatorial positions at the six-membered ring. The packing of all three structures involves chains of molecules with offset stacking of the AuX3 moieties associated with short Au...X contacts; for 1 and 2b these are reinforced by N—H...X hydrogen bonds, whereas for 2a there are no classical hydrogen bonds and the chains are interconnected by Br...Br contacts.

Abstract Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.

Von einer qualitätsvollen Medienberichterstattung wäre gemäß Public-Interest-Modell der normativen Medientheorie zu erwarten, dass sie sexuellen Kindesmissbrauch (SKM) als relevantes soziales Problem regelmäßig auf die Agenda setzt und in einer qualitätsvollen Weise behandelt, die zur gesellschaftlichen Sensibilisierung und Problemlösung beiträgt. Vor diesem Hintergrund war es Ziel der vorliegenden Arbeit, erstmals die Qualität der SKM-Berichterstattung in der deutschsprachigen Presse zu analysieren. Die Analyse konzentrierte sich auf die Berichterstattung über SKM an der Odenwaldschule, da es sich um einen gut aufgeklärten Fall institutionellen Missbrauchs in Deutschland mit großer Tragweite und Medienresonanz handelt. Beantwortet werden sollten zwei Forschungsfragen: Welche etablierten journalistischen Qualitätskriterien (QK) erfüllt bzw. verletzt die SKM-Berichterstattung über die Odenwaldschule (F1)? Welche Qualitätsunterschiede gibt es in der SKM-Berichterstattung zwischen Qualitäts- und Boulevardpresse (F2)? Eine zweistufige bewusste Stichprobe von N = 325 Zeitungsartikeln über SKM an der Odenwaldschule (2010-2022; 23 Print- und Online-Zeitungen, 52.3 % Qualitätspresse, 47.7 % Boulevardpresse) wurde anhand eines Codebuchs einer Qualitätsanalyse unterzogen. Das deduktiv entwickelte und induktiv verfeinerte Codebuch bestand aus 12 formalen und 20 inhaltlichen Kategorien und zeigte eine hohe Reliabilität (Gwets AC1: 0.82 – 1.00). Die Datenanalyse erfolgte deskriptiv- und inferenzstatistisch mit der Software R. Die Studie ist präregistriert und alle Daten, Analyseskripte und Zusatzmaterialien sind auf OSF öffentlich zugänglich (https://osf.io/j5wcn). Es zeigte sich, dass in der SKM-Berichterstattung über die Odenwaldschule die meisten journalistischen QK erfüllt wurden, während gleichzeitig drei Qualitätsprobleme sichtbar waren: die mangelnde Thematisierung von Prävention und Intervention, eine sensationalistische Darstellung sowie die Nutzung unangemessener Begriffe (F1). Diese Probleme traten in der Qualitäts- und Boulevardpresse vergleichbar auf. Bei keinem Qualitätskriterium waren signifikante Unterschiede zwischen Qualitäts- und Boulevardpresse beobachtbar (F2). In Erweiterung des bisherigen Forschungsstandes zeigt die vorliegende Studie Verbesserungsbedarf in der SKM-Berichterstattung auf – und zwar in der Qualitäts- und Boulevardpresse gleichermaßen. Dass die Boulevardpresse nicht schlechter abschnitt, lässt sich damit erklären, dass sie in der Berichterstattung über SKM an der Odenwaldschule relativ häufig offen oder verdeckt auf Presseagenturmeldungen zurückgriff, deren Qualität in der Regel höher ist als bei der typischen boulevardesken Berichterstattung. Konsequenzen für die Forschung und Praxis werden diskutiert.

As a neurodevelopmental multifactorial disorder whose prevalence has been increasing worldwide, attention-deficit hyperactivity disorder (ADHD) is considered a public health concern. Methylphenidate (MPH) is the drug of choice for ADHD; however, not all patients respond fully to this treatment. Therefore, exploring the underlying molecular mechanisms involved in ADHD and potential novel therapeutic targets is crucial. Here, we generated induced pluripotent stem cells (iPSCs) from Peripheral Blood Mononuclear Cells (PBMCs) retrieved from four ADHD patients (two MPH responders and two non-responders) using Sendai virus. These lines might be helpful for the in vitro investigation of ADHD pathophysiology in a patient-specific manner.

Objectives To evaluate the long-term effectiveness and safety of autologous haematopoiesis stem cell transplantation (AHSCT) for severe, refractory autoimmune diseases in paediatric patients.Methods A single-centre study of consecutive children and adolescents with refractory autoimmune diseases undergoing AHSCT was performed. Demographics, clinical, laboratory features, pre-AHSCT medications, disease activity and functional status were captured. The primary outcome was progression-free survival, secondary outcomes included overall survival, disease-specific treatment responses, disease activity at the last follow-up and AHSCT safety.Results The study included seven patients: two systemic sclerosis, one pansclerotic morphoea, one eosinophilic fasciitis, one juvenile dermatomyositis and two patients with systemic juvenile idiopathic arthritis; four women, three men median age at AHSCT of 10 years (7–19), median follow-up post-AHSCT of 17 years. Median progression-free survival and overall survival was 4.2 years (95% CI: 0.98 to 8.3) and 17 years (95% CI: 11.8 to 22.1), respectively. Progression-free survival rates at 1 and 2 years post-AHSCT were 100% and 77%, respectively. All children survived. All patients are in clinical remission, only four require ongoing immunotherapy. Safety: Three experienced infections, including HHV6, Candida and Ralstonia sepsis; one developed a systemic inflammatory response syndrome; two new onset secondary autoimmune diseases including autoimmune haemolytic anaemia, Graves’ disease and one was found to have a breast fibroadenoma. Treatment toxicity: one cyclophosphamide-associated transient renal failure and pericardial effusion, one patient with amenorrhoea/infertility.Conclusions AHSCT was an effective and safe approach for children and adolescents with treatment-refractory autoimmune diseases. The indication and timing of transplantation requires a careful consideration and a multidisciplinary approach.

While intensive control of weed populations plays a central role in current agriculture, numerous studies highlight the multifaceted contribution of weeds to the functionality and resilience of agroecosystems. Recent research indicates that increased evenness within weed communities may mitigate yield losses in contrast to communities characterized by lower diversity, since weed species that strongly affect crop yields, also dominate weed communities, with a concurrent reduction of evenness. If confirmed, this observation would suggest a paradigm shift in weed management towards promoting higher community diversity. To validate whether the evenness of weed communities is indeed linked to higher crop productivity, we conducted two field experiments: one analyzing the effects of a natural weed community in an intercrop of faba bean and oat, and the other analyzing the effects of artificially created weed communities, together with the individual sown weed species, in faba bean, oats and an intercrop of both crops. The evenness of the weed communities ranged from 0.2 to 0.9 in the natural weed community, from 0.2 to 0.7 in faba bean, from 0 to 0.8 in the intercrop and from 0.3 to 0.9 in oats. Neither the natural nor the artificial weed community showed significant effects of evenness on crop grain yield or crop biomass. The results of this study do not validate a positive relationship of crop productivity and weed evenness, possibly due to low weed pressure and the absence of competitive effects but suggest that also less diverse weed communities may be maintained without suffering yield losses. This is expected to have far reaching implications, since not only diverse weed communities, but also higher abundances of few weed species may contribute to ecosystem functions and may support faunal diversity associated with weeds.

Face-to-face participatory research and interaction is at the heart of empirical social research. The COVID-19 pandemic and the resulting physical distance restrictions had a significant impact on qualitative research. Instantly, conventional qualitative social science methods had to be adapted to ‘remote’ and digital modes of interaction. The focus of this article is to analyze how and why video-mediated formats such as online conference tools and online whiteboards affect personal interaction, cooperation, collaboration and data acquisition. In a retrospective process, we first inductively defined three characteristics of interaction, namely emplacement, communication and rapport. Conducting research about climate adaptation in coastal regions touches upon a sensitive and emotional topic. Emplacement is a decisive characteristic to understand how identities are built. The combination of verbal and non-verbal communication leads to contextualization, and building rapport is essential for trustful collaboration. To answer the question if video-mediated formats enable a replacement of face-to face formats, we deductively analyze the implications of video-mediated formats used in semi-structured interviews, qualitative social network analysis and focus groups on these characteristics. Our analysis reveals that video-mediated formats are sufficient to gather information but hamper crucial relational and trust-building processes. This implies that, by using video-mediated formats, the content level was hardly exceeded. Compared to face-to-face formats, non-verbal communication, emplacement and rapport are limited using digital formats, with problematic consequences for data generation and its understanding as well as for interaction in terms of trust, lasting relationships, knowledge generation and liability. In brief: Video-mediated formats hold the danger that research is done about participants and not with participants.

The etiology of pediatric acute lymphatic leukemia (ALL) is still unclear. Whole-metagenome shotgun sequencing of bone marrow samples in patients with treatment-naïve ALL (n=6) was performed for untargeted investigation of bacterial and viral DNA. The control group consisted of healthy children (n=4) and children with non-oncologic diseases (n=2) undergoing bone marrow sampling. Peripheral blood of all participants was investigated at the same time. After bioinformatical elimination of potential contaminants by comparison with the employed controls, no significant amounts of microbial or viral DNA were identified.

This paper investigates how lecturers’ connectedness with students affected their experience of online teaching during the first COVID-19 lockdown in the UK and Switzerland. We examined how this connectedness predicted lecturers’ self-efficacy in online teaching. This was in addition to other social context variables (connectedness with colleagues and perceived support from the university) and their previous experience with digital tools. The shift to online teaching in the lockdown period abruptly removed any in-person contact between lecturers and their students. Lecturers’ self-efficacy in online teaching is crucial to student motivation, achievement, and the lecturer's own teaching experience. Likewise, lecturers’ connectedness with students and colleagues has been identified as a key factor in learning. Consequently, this study explored how different forms of connectedness predicted lecturers’ self-efficacy in the new teaching environment. A total of 252 lecturers from UK and Swiss universities completed an online survey about their teaching experiences before and during the COVID-19 lockdown. Multiple regressions were used to predict lecturers’ online teaching self-efficacy. The results revealed that connectedness with students was a significant and positive predictor of online teaching self-efficacy. However, connectedness with colleagues and perceived support from the university did not. The perception that digital tools enhanced teaching prior to the lockdown was a significant predictor only for the UK lecturers, but not for the Swiss ones. These findings point towards lecturers’ connectedness with their students being a pathway to success in online teaching.

In 2020, for the first time in history, COVID-19 measures necessitated emergency online teaching to ensure continuity of education. Although institutional support was offered to lecturers, the situation posed an extraordinary challenge for university teaching. Using a comparative approach, this study surveys lecturers from different countries and their use of educational technology for emergency online teaching. Its focus lies on the relationships between use of educational technology, online teaching self-efficacy and attitudes towards educational technology. Overall and according to reports, the use of educational technology increased significantly compared to pre-pandemic conditions. The universities studied had different levels of digitalization, which influenced lecturers' use of educational technology. Furthermore, lecturers differed in terms of self-efficacy, attitude, and perception. Regarding factors affecting educational technology use, results showed that especially pre-pandemic experiences with educational technology, as well as self-efficacy and perceptual variables influenced the use of educational technology during the pandemic. Based on these results, it is advisable for universities to embrace this ad hoc switch to online teaching as an opportunity for purposeful digitalization of university teaching.

Abstract Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7–2.0 times cheaper than standard WES (no-plexing), 1.8–2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

In bis(4-methylpiperidine-κN)gold(I) chloride, [Au(C6H13N)2]Cl (1), the methyl groups are, as expected, equatorial at the piperidine ring, but the Au atom is axial; this is the case for all five structures reported here, as is the expected linear coordination at the Au atom. Hydrogen bonding of the form N—H...Cl−...H—N leads to inversion-symmetric dimers, which are further connected by C—H...Au contacts. Bis(4-methylpiperidine-κN)gold(I) dichloridoaurate(I), [Au(C6H13N)2][AuCl2] (2), also forms inversion-symmetric dimers; these involve aurophilic interactions and three-centre hydrogen bonds of the form NH(...Cl)2. Bis(4-methylpiperidine-κN)gold(I) dibromidoaurate(I), [Au(C6H13N)2][AuBr2] (3), is isotypic to 2. The 1:1 adduct chlorido(4-methylpiperidine-κN)gold(I) bis(4-methylpiperidine-κN)gold(I) chloride, [Au(C6H13N)2]Cl·[AuCl(C6H13N)] (4), crystallizes as its dichloromethane solvate. The asymmetric unit contains two formula units, in each of which the chloride anion accepts a hydrogen bond from the cation and from the neutral molecule, and the two Au atoms are linked via an aurophilic interaction. A further hydrogen bond leads to inversion-symmetric dimers. The asymmetric unit of bis(2-methylpiperidine-κN)gold(I) chloride, [Au(C6H13N)2]Cl (5), contains two `half' cations, in which the Au atoms lie on twofold axes, and a chloride ion on a general position. Within each cation, the relative configurations at the atoms N and C2 (which bears the methyl substituent) are R,S. The twofold-symmetric dimer involves two N—H...Cl−...H—N units and an aurophilic contact between the two Au atoms.

The demand for industrial enzymes is continually rising, fueled by the growing need to shift towards more sustainable industrial processes. However, making efficient enzyme production strains and identifying optimal enzyme expression conditions remains a challenge. Moreover, the production of the enzymes themselves comes with unavoidable impacts, e.g., the need to utilize secondary feedstocks. Here, we take a more holistic view of bioprocess development and report an integrative approach that allows us to rapidly identify improved enzyme expression and secretion conditions and make use of cyanobacterial waste biomass as feed for supporting Pichia pastoris fermentation. We demonstrate these capabilities by producing a phytase secreted by P. pastoris that is grown on cyanobacterium hydrolysate and buffered glycerol-complex (BMGY) medium, with genetic expression conditions identified by high-throughput screening of a randomized secretion library. When our best-performing strain is grown in a fed-batch fermentation on BMGY, we reach over 7 000 U/mL in three days.

Periprosthetic joint infections (PJI) are a common reason for orthopedic revision surgeries. It has been shown that the silver surface modification of a titanium alloy (Ti–6Al–4V) by PMEDM (powder mixed electrical discharge machining) exhibits an antibacterial effect on Staphylococcus spp. adhesion. Whether the thickness of the silver-modified surface influences the adhesion and proliferation of bacteria as well as the ossification processes and in-vivo antibacterial capacity has not been investigated before. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process depending on the thickness of PMEDM silver modified surfaces.The attachment of S. aureus on the PMEDM modified surfaces was significantly lower than on comparative control samples, independently of the tested surface properties. Bacterial proliferation, however, was not affected by the silver content in the surface layer. We observed a long-term effect of antibacterial capacity in vitro, as well as in vivo. An induction of ROS, as indicator for oxidative stress, was observed in the bacteria, but not in osteoblast-like cells. No influence on the in vitro osteoblast function was observed, whereas osteoclast formation was drastically reduced on the silver surface. No changes in cell death, the metabolic activity and oxidative stress was measured in osteoblasts.We show that already small amounts of silver exhibit a significant antibacterial capacity while not influencing the osteoblast function. Therefore, PMEDM using silver nano-powder admixed to the dielectric represents a promising technology to shape and concurrently modify implant surfaces to reduce infections while at the same time optimizing bone ingrowth of endoprosthesis.

The compounds bis(morpholine-κN)gold(I) chloride, [Au(C4H9NO)2]Cl, 1, and bis(morpholine-κN)gold(I) bromide, [Au(C4H9NO)2]Br, 2, crystallize isotypically in space group C2/c with Z = 4. The gold atoms, which are axially positioned at the morpholine rings, lie on inversion centres (so that the N—Au—N coordination is exactly linear) and the halide anions on twofold axes. The residues are connected by a classical hydrogen bond N—H...halide and by a short gold...halide contact to form a layer structure parallel to the bc plane. The morpholine oxygen atom is not involved in classical hydrogen bonding.

Objective: Nimodipine still represents a unique selling point in the prevention of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Its intrathecal effect is limited by a low oral bioavailability, leading to the development of nanocarrier systems to overcome this limitation. This study investigated the ultrasound-induced release profile of nimodipine from drug-loaded copolymers in artificial cerebrospinal fluid (CSF) within 72 h after a singular versus repeated sonication. Methods: Pluronic® F127 copolymers (Sigma-Aldrich, Taufkirchen, Germany)were loaded with nimodipine by direct dissolution. Spontaneous and on-demand drug release by ultrasound (1 MHz at 1.7 W/cm2) was determined in artificial cerebrospinal fluid using the dialysis bag method. Nimodipine concentrations were measured at predefined time points within 72 h of sonication. Results: Spontaneous release of nimodipine was enhanced by ultrasound application with significantly increased nimodipine concentrations two hours after a repeated sonication compared to a singular sonication (median 1.62 vs. 17.48 µg/µL, p = 0.04). A further trend was observed after four hours (median 1.82 vs. 22.09 µg/µL, p = 0.06). There was no difference in the overall nimodipine concentrations between the groups with a singular versus repeated sonication (357.2 vs. 540.3 µg/µL, p = 0.60) after 72 h. Conclusions: Repeated sonication resulted in an acceleration of nimodipine release from the drug-loaded copolymer in a CSF medium. These findings confirm the proof of principle of an on-demand guidance of nimodipine release from nimodipine-loaded nanodrugs by means of ultrasound, which suggests that evaluating the concept in an animal model may be appropriate.