Search

Enzymes are capable of unique and selective transformations that can enable sustainable chemical production. While many industrial processes have been developed using free enzymes in aqueous solutions, immobilizing enzymes on a solid support can offer considerable advantages, including improved reaction efficiency, enzyme stability, the ability to perform reactions in non-aqueous media, and simplified separation of product from enzyme. Herein, we describe the development of a biocatalytic transaminase reaction of CyreneTM (2) utilizing an immobilized, evolved transaminase enzyme in an organic solvent to provide amine intermediate 3a en route to the Brutons tyrosine kinase (BTK) inhibitor nemtabrutinib. Enzyme immobilization is critical to facile isolation of the water-soluble product. Improved reaction kinetics and diastereoselectivity were achieved by bridging directed enzyme evolution with the selection of an optimal reaction solvent and solid support for immobilization, enabling a unified solvent system and direct isolation of 3a as a crystalline salt with dr > 50:1.

Nowadays teenagers grow up with social media and various possibilities of digital communication. The offline and online lives of “digital natives” are tightly bound together and for most of them life without Internet is unthinkabe. However, what happens when teenagers do not have access to modern communication facilities and to social media? Do they miss these media? What services and which activities do teenagers miss? We gathered qualitative data from teenagers after three weeks of being completely offline in frames of a long-term adventure education program. We also gathered quantitative data on teenage media use before media withdrawal. 135 teenagers (M=14.47, SD=.56, 52% female) answered our questions within four years (34 teenagers in each of these years - 2018, 2019, 2020 - and 33 teenagers in 2021). After three weeks of complete media withdrawal two thirds of teenagers reported not missing social media or missing them to a minor extent. They described social media services as stressful, disturbing, extremely time-consuming and boredom-related. Several respondents replied that they had enough communication offline and felt good in the community that made online social media superfluous. However, every third teenager reported missing social media. The main reason was the desire to contact the personal social network. A few teenagers reported missing social media as a source of relaxation and an efficient way to “switch-off”. One out of four teenagers (23%) reported missing WhatsApp. One out of ten (11%) mentioned Instagram, but just one half in a context of missing it. WhatsApp and Instagram were also the most popular services among teenagers before withdrawal (94.3% of teenagers reported having a profile in WhatsApp and 73,3% of teenagers reported using Instagram). Only a few teenagers (2.2%) - all boys - mentioned missing YouTube. The article presents further results, discusses perspectives and limitations of the project.

Introduction Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be below 50%. Methods Since epigenetics of the stress response system seem to play a role in MDD, we analyzed the DNA methylation (DNAm) of genes encoding the glucocorticoid receptor (NR3C1) and proopiomelanocortin (POMC) through Sanger Sequencing. For analysis, blood was taken before and after the first and last ECT from MDD patients (n=31), unmedicated depressed controls (UDC; n=19, baseline), and healthy controls (HC; n=20, baseline). Results Baseline DNAm in NR3C1 was significantly lower in UDCs compared to both other groups (UDC: 0.014(±0.002), ECT: 0.031(±0.001), HC: 0.024(±0.002); p Discussion Our findings indicate that both genes might play a role in the chronification of depression and NR3C1 may be relevant for ECT response prediction.

Contains fulltext : 290548.pdf (Publisher’s version ) (Open Access)

Abstract Over the last decades, numerous natural habitats have been converted into settlement areas, agricultural land, and tree plantations on a large spatial scale. As a result, natural ecosystems have been destroyed. In consequence, many ecosystems exist today as small and geographically isolated remnants. To what extent the original species diversity can persist in such small habitat patches is questionable and strongly depends on the ecology of the species. A prominent example of severe habitat destruction are the species-rich tropical cloud forests of Taita Hills in southern Kenya, which have been deforested almost completely during past decades. However, there still exist typical forest species in the few remaining forest fragments. In this study, we investigate the population ecology and behaviour of two butterfly species present in the cloud forest remnants of Taita Hills, Protogoniomorpha parhassus and Precis tugela. Over a period of one month, we conducted Mark-Release-Recapture to study population sizes and demographic structures, lifespan, dispersal, and behaviour. We found that both species exhibited medium population sizes and are sedentary. However, some individuals performed dispersal throughout the forest. The behaviour of the two species differs: While P. tugela was mostly observed basking with open wings, P. parhassus was mostly sitting under leaves with closed wings. The life span was rather long for butterflies. Implications for insect conservation This study documents the population ecology and behaviour of these two Afrotropical butterflies and underlines the relevance of the conservation of cloud forest remnants to preserve species, which mainly depends on these habitat remnants.

Hepatitis B virus (HBV) was identified as an enveloped DNA virus with a diameter of 42 nm. Multivesicular bodies play a central role in HBV egress and exosome biogenesis. In light of this, it was studied whether intact virions wrapped in exosomes are released by HBV-producing cells.Robust methods for efficient separation of exosomes from virions were established. Exosomes were subjected to limited detergent treatment for release of viral particles. Electron microscopy of immunogold labeled ultrathin sections of purified exosomes was performed for characterization of exosomal HBV. Exosome formation/release was affected by inhibitors or Crispr/Cas-mediated gene silencing. Infectivity/uptake of exosomal HBV was investigated in susceptible and non-susceptible cells.Exosomes could be isolated from supernatants of HBV-producing cells, which are characterized by the presence of exosomal and HBV markers. These exosomal fractions could be separated from the fractions containing free virions. Limited detergent treatment of exosomes causes stepwise release of intact HBV virions and naked capsids. Inhibition of exosome morphogenesis impairs the release of exosome-wrapped HBV. Electron microscopy confirmed the presence of intact virions in exosomes. Moreover, the presence of large hepatitis B virus surface antigen on the surface of exosomes derived from HBV expressing cells was observed, which conferred exosome-encapsulated HBV initiating infection in susceptible cells in a , large hepatitis B virus surface antigen/NaThese data indicate that a fraction of intact HBV virions can be released as exosomes. This reveals a so far not described release pathway for HBV.

A bidirectional Pictet-Spengler Reaction allows easy access to nitrogen-rich aromatics with seven fused rings. Photophysical measurements and computational methods show significant differences to parent N-heteropolycycles with fewer nitrogen atoms.

Os desequilíbrios musculares e funcionais são analisados na tentativa de prevenir lesões e melhorar os desempenhos de atletas. Objetivo: Analisar o desempenho muscular de extensores e flexores de joelho e o desempenho funcional dos membros inferiores de atletas de voleibol. Métodos: Quinze atletas da categoria sub-16 de voleibol feminino da Universidade de Caxias do Sul foram avaliadas. Para análise do desempenho muscular, as variáveis pico de torque de extensores e flexores de joelho, e razão convencional de extensores/flexores, foi utilizado o dinamômetro isocinético. Já para a análise funcional dos membros inferiores, foram utilizados os testes Hop tests e Y balance test (YBT). Resultados: Na comparação entre membro dominante (MD) e não dominante (MND), não houve diferenças estatisticamente significativas na análise do pico de torque; já na razão flexores/extensores foi encontrada diferença significativa apenas à 240°/s. Entretanto, os valores médios da razão flexores/extensores encontrarem-se abaixo dos valores sugeridos pela literatura. As avaliações funcionais também não mostraram assimetrias entre os membros; no entanto, a pontuação composta do YBT apresentou-se abaixo dos valores normativos. Conclusão: A excelente simetria entre os membros pode ser justificada pela especificidade do esporte, pois os gestos esportivos do voleibol apresentam carácter simétrico durante as exigências físicas dos membros inferiores. No entanto, os baixos valores da razão flexores/extensores e da pontuação composta do YBT talvez não estejam diretamente relacionados a um risco maior de lesões já que os valores de referência utilizados são de atletas adultos.

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3–8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.

Zusammenfassung Gegenstand und Ziel Ziel dieser Studie ist es, die Modified Maquet Procedure (MMP) mit der Tibial Plateau Leveling Osteotomy (TPLO) anhand von Langzeitkontrollen über ein Jahr (∅ 3,15 Jahre) mittels klinischer Untersuchung, röntgenologischer Beurteilung der Arthroseprogression und Ganganalyse durch Laufbanduntersuchung zu vergleichen. Zusätzliches Ziel ist es, den Einfluss der Erfahrung der Chirurgen bei der TPLO-Technik zu überprüfen. Material und Methoden Bei dieser klinischen Studie wurden 67 Kniegelenke von 50 Hunden verschiedener Rassen zwischen 20 und 40 Kilogramm Körpergewicht einbezogen, die mittels TPLO beziehungsweise MMP (n = 19) nach Ruptur des vorderen Kreuzbandes operiert wurden. Die TPLO-Gruppe unterteilte sich in eine Gruppe, welche von 2 erfahrenen Chirurgen (TPLO1, n = 25) operiert wurde und eine zweite Gruppe, die von mehreren Chirurgen unterschiedlicher Erfahrung (TPLO2, n = 23) versorgt wurden. Die Hunde wurden nach mindestens über einem Jahr (3,15 ± 1,21 Jahre) postoperativ orthopädisch, röntgenologisch und ganganalytisch uni- und bilateral getrennt untersucht. Zusätzlich wurden die Daten der Ganganalyse mit einer orthopädisch gesunden Kontrollgruppe verglichen. Ergebnisse Bei der orthopädischen Untersuchung wurden keine signifikanten und klinisch relevanten Unterschiede zwischen den 3 Gruppen festgestellt.Die Arthroseprogression zeigte in allen 3 OP-Gruppen ähnliche Werte, wobei die der TPLO2-Gruppe durchschnittlich pro Jahr gerechnet signifikant etwas geringer war als die der TPLO1- und der MMP-Gruppe.Die ganganalytische Untersuchung im Schritt konnte vor allem im Vergleich mit der gesunden Kontrollgruppe signifikante Unterschiede bei bilateralen Rupturen für die Peak Vertical Force und den Vertical Impulse zeigen. Die Standphasendauer wies keine signifikanten Unterschiede auf. Im Trab konnten keine signifikanten Unterschiede zwischen den 3 OP-Gruppen festgestellt werden. Schlussfolgerung Beide Operationstechniken erzielten in den 3 Gruppen bei den Langzeitkontrollen gute klinische, radiologische und ganganalytische Ergebnisse auch im Vergleich mit einer gesunden Kontrollgruppe. Klinische Relevanz Die MMP kann als schnell durchführbare Alternative zur etablierten TPLO mit ebenfalls guten Ergebnissen beim Hund angesehen werden. Die Erfahrung des Chirurgen scheint keinen Einfluss auf das Ergebnis zu haben.

Background: A disruption of sebocyte differentiation and lipogenesis has fatal consequences and can cause a wide spectrum of skin diseases, from acne vulgaris to sebaceous carcinoma, however, the relevant molecular mechanisms have not been fully clarified. Objectives: The induction of autophagy and apoptosis in human sebocytes in response to biologically relevant fatty acids was investigated. Methods: Free fatty acids (arachidonic acid, linoleic acid, palmitic acid, and palmitoleic acid) and the pan-caspase inhibitor QVD-Oph were added to the supernatant of cultured human SZ95 sebocytes. Individual relevant proteins were analyzed by Western blotting. Apoptosis and cell viability were determined, and typical autophagy structures were detected through electron microscopy. To obtain cell growth curves, cell confluence was continuously monitored by real-time cell analysis. Results: Fatty acids induced the development of intracellular lipid droplets with subsequent apoptosis, whereas arachidonic acid caused the most rapid effect. Cleavage products of caspase-3 were only detected in arachidonic acid-induced apoptosis. The high basal apoptotic rate of cultured SZ95 sebocytes was strongly suppressed by QVD-Oph. Fatty acid-induced apoptosis was also markedly inhibited by QVD-Oph, whereas intracellular lipid droplets further accumulated. While cell viability after incubation with linoleic acid, palmitic acid, or palmitoleic acid and QVD-Oph was comparable with that of non-treated controls, arachidonic acid significantly reduced cell viability and cell density despite the concomitant pan-caspase inhibitor treatment. Using electron microscopy, typical autophagy structures were detected, such as autophagosomes and autolysosomes, at the basal level, which became more pronounced after treatment with fatty acids. Conclusions: Our findings contribute to a better understanding of the inflammation-associated mechanisms of lipogenesis and cell death induction in human sebocytes and may help to unveil the effects of fatty acid-rich human nutrition.

Graph Neural Networks (GNNs) are a popular approach for predicting graph structured data. As GNNs tightly entangle the input graph into the neural network structure, common explainable AI approaches are not applicable. To a large extent, GNNs have remained black-boxes for the user so far. In this paper, we show that GNNs can in fact be naturally explained using higher-order expansions, i.e. by identifying groups of edges that jointly contribute to the prediction. Practically, we find that such explanations can be extracted using a nested attribution scheme, where existing techniques such as layer-wise relevance propagation (LRP) can be applied at each step. The output is a collection of walks into the input graph that are relevant for the prediction. Our novel explanation method, which we denote by GNN-LRP, is applicable to a broad range of graph neural networks and lets us extract practically relevant insights on sentiment analysis of text data, structure-property relationships in quantum chemistry, and image classification., Comment: 14 pages + 6 pages supplement

The recent development of the TOUGH3 code allows for a faster and more reliable fluid flow simulator. At the same time, new versions of FLAC3D are released periodically, allowing for new features and faster execution. In this paper, we present the first implementation of the coupling between TOUGH3 and FLAC3Dv6/7, maintaining parallel computing capabilities for the coupled fluid flow and geomechanical codes. We compare the newly developed version with analytical solutions and with the previous approach, and provide some performance analysis on different meshes and varying the number of running processors. Finally, we present two case studies related to fault reactivation during CO2 sequestration and nuclear waste disposal. The use of parallel computing allows for meshes with a larger number of elements, and hence more detailed understanding of thermo-hydro-mechanical processes occurring at depth., Computational Geosciences, 26 (6), ISSN:1420-0597, ISSN:1573-1499

La metahemoglobinemia es una condición caracterizada por la presencia de altas concentraciones de metahemoglobina en sangre, la cual es incapaz de liberar oxígeno a los tejidos. Es una entidad poco frecuente, con baja sospecha diagnóstica, y puede ser adquirida o hereditaria. Dentro de las formas hereditarias, se encuentran la hemoglobina M y lametahemoglobinemia recesiva congénita. Ésta última causada por el déficit de la enzima NADH citocromo b5 reductasa (B5R), como consecuencia de alteraciones bialélicas en el gen CYB5R3.Reportamos las características clínicas, hematológicas y moleculares de una recién nacida con diagnóstico de deficiencia de B5R. La niña presentó cianosis en las primeras horas de vida, con niveles elevados de metahemoglobina. Luego de descartar las causas pulmonares, cardíacas, infecciosas y adquiridas se arribó al diagnóstico por la secuenciación del gen CYB5R3. Resaltamos la importancia de reconocer la causa de la metahemoglobinemia para dar un tratamiento y consejo genético adecuados.

Determining how infrastructure corridors are to be designed optimally and modified over time is challenging due to the considerable uncertainty associated with potential changes in mobility patterns. This is due to factors such as the dynamisms of urban areas and the potential of transitioning to autonomous vehicles. Although currently this future uncertainty is taken into consideration in decisions with respect to highway designs and modifications in a qualitative manner, there is potential benefit to using quantitative methods and explicitly considering how highways may be modified in the future as a function of the actual future that emerges. In this paper, the use of a quantitative evaluation method using real options is explored to evaluate highway designs, considering uncertainties in future mobility patterns and management flexibility. The usefulness of the method is investigated on the fictive but realistic case study based on the completion of the A15 highway, in the canton of Zurich, Switzerland. The results of this exploratory work indicate significant value in the use of the proposed method to ensure that infrastructure networks are optimally prepared to support society in an unknown future, and it is expected that it can be used more extensively in future spatial planning.

Fungal infections have increased considerably over the last decades, becoming progressively resistant to common drugs. UVC light has shown microbiological eradication effects, whereby the wavelength of 254 nm is strongly carcino- and mutagenic. Therefore, 222 and 233 nm, which do not significantly harm skin cells, were tested for their antifungal effects. Microbicidal doses were reached at 40 mJ/cm

A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.

PurposeThe present research had the objectives of proposing, testing and validating a theoretical model that includes ecological awareness, healthy consumption, consumer attitude and price awareness as determinants of the purchase intention of organic foods and analyzing the moderating effect of gender, educational level and income of families in the relationship between price awareness and purchase intention.Design/methodology/approachA survey research was implemented with 382 Brazilians who consume organic foods from a non-probabilistic sample for convenience. For data analysis, structural equation modeling was used to test the proposed theoretical model and its respective relationships.FindingsThe results showed that ecological awareness, healthy consumption, consumer attitude and price awareness are determinants of the purchase intention of organic foods 79.1% of the variance of purchase intention of organic foods could be explained by such determinants. Another relevant result is that gender and family income has a positive moderating effect on the relationship between price awareness and the intention to purchase organic food.Originality/valueEnvironmental problems and their adverse impacts on humans have become an important issue to be analyzed by academics (researchers), governments and organizations, and their managers, especially when organic foods are considered.

Tandem repeat (TR) variation is associated with gene expression changes and over 50 rare monogenic diseases. Recent advances in sequencing have enabled accurate, long reads that can characterize the full-length sequence and methylation profile of TRs. However, despite these advances in sequencing technology, computational methods to fully profile tandem repeats across the genome do not exist. To address this gap, we introduce tools for tandem repeat genotyping (TRGT), visualization and an accompanying TR database. TRGT accurately resolves the length and sequence composition of TR regions in the human genome. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of 99.56%, allowing a single repeat unit difference. In six samples with known repeat expansions, TRGT detected all repeat expansions while also identifying methylation signals, mosaicism, and providing finer resolution of repeat length. Additionally, we release a database with allele sequences and methylation levels for 937,122 TRs across 100 genomes.

The factors driving initiation of pathological expansion of tandem repeats remain largely unknown. Here, we assessed theFGF14-SCA27B (GAA)•(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a 5’-flanking 17-bp deletion-insertion in 70.34% of alleles (3,463/4,923). This common sequence variation was present nearly exclusively on alleles with fewer than 30 GAA-pure repeats and was associated with enhanced meiotic stability of the repeat locus.

Increased vulnerability to stress is a major risk factor for the manifestation of several mood disorders, including major depressive disorder (MDD). Despite MDD’s status as a significant donor to global disability, the complex integration of genetic and environmental factors that contribute to the behavioral display of such disorders has made a thorough understanding of related etiology elusive. Recent developments suggest that a brain-wide network approach is needed, taking into account the complex interplay of cell types spanning multiple brain regions. Single cell RNA-sequencing technologies can provide transcriptomic profiling at the single-cell level across heterogenous samples. Furthermore, we have previously used local field potential oscillations and machine learning to identify an electrical brain network that is indicative of a predisposed vulnerability state. Thus, this study combined single cell RNA-sequencing (scRNA-Seq) with electrical brain network measures of the stress-vulnerable state, providing a unique opportunity to access the relationship between stress network activity and transcriptomic changes within individual cell types. We found especially high numbers of differentially expressed genes between animals with high and low stress vulnerability brain network activity in astrocytes and glutamatergic neurons but we estimated that vulnerability network activity depends most on GABAergic neurons. Furthermore, we found that genes significantly upregulated in animals with higher vulnerability brain network activity across multiple cell types included upregulation of microglia activity, mitochondrial and metabolic pathways, and those with lower vulnerability network activity included pathways involved in synapse regulation.Abstract Figure

International audience; Background Recent improvements in spatial resolution and measurement sensitivity for high-resolution digital image cor-relation (HR-DIC) now provide an avenue for the quantitative measurement of deformation events and capturing the physicalnature of deformation mechanisms. However, HR-DIC measurements require significant time due to scanning electron imageacquisition; such a limitation prevents the widespread use of HR-DIC for material characterization.Objective Apply a novel SEM acquisition technology to enhance HR-DIC measurements for high throughput applications.Methods Multi-beam SEM technology is employed to image an entire gauge length at once at high resolution and at nearly ahundredfold acceleration of typical HR-DIC image acquisition, even when automated stage movement and image acquisitionare employed. These images were fed into a discontinuity-tolerant HR-DIC software to determine slip localization inducedby non-metallic inclusions and grain structure.Results Slip localization was able to be analyzed to an unprecedented level, with over 210,000 slip bands able to be investi-gated, with the most intense slip localizing near and parallel to twin boundaries and in the vicinity of non-metallic inclusionclusters. Additionally, secondary slip activation and grain boundary shearing by intense dislocation pileups are observed toreduce slip amplitude near and parallel to twin boundaries.Conclusions By performing HR-DIC in conjunction with a multi-beam SEM, high-throughput measurements of large field-of-view, high-resolution images were able to be performed in a timely manner. These measurements provided an immensenumber of slip events for statistical analysis to be performed on to relate to microstructural features.

BackgroundIn diploid organisms, phasing is the problem of assigning the heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation such as structural variants. However, current phasing tools typically only phase small variants, leaving larger structural variants unphased.MethodsWe developed HiPhase, a tool that jointly phases SNVs, indels, and structural variants. The main benefits of HiPhase are 1) dual mode allele assignment for detecting structural variants, 2) a novel application of the A*-algorithm to phasing, and 3) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions.ResultsIn our assessment, HiPhase produced an average phase block NG50 of 493 kb with 933 switchflip errors and fully phased 95.2% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, and structural variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.Availabilityhttps://github.com/PacificBiosciences/HiPhase

Radiofrequency ablation (RFA) is subject to "heat-sink" effects, particularly for treatment of tumors adjacent to major vessels.In this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4-8.5) for HCC, 6.4 cm (0.5-11) for ICC and 3.8 cm (0.5-13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival.The overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively.SRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence.

Context Intensification of land-use caused a reduction of ecosystem heterogeneity and diversity, and subsequently led to dramatic decrease of biodiversity. Species depending on dynamic ecosystems are particularly affected from this trend of land-use intensification, landscape homogenization, and the optimization of land-use. Forest species suffer under the intensification of forest management, in the worst case transforming light and heterogeneous deciduous forests into species-poor intensively used deciduous forests optimized for wood production. This lead to the destruction of a mosaic consisting of various successional stages in parallel. Objective In this study we analyse the relevance of forest heterogeneity, forest disturbance and microhabitat preferences of egg oviposition and larval development for a highly endangered butterfly species, Euphydryas maturna. This butterfly species mainly occurs in light and moist deciduous forests, such as riparian forests along mountain streams in northern Austria. Methods We combine detailed field observations with high resolution aerial pictures taken with an Unmanned Aerial Vehicle (UAV) to build ensemble habitat suitability models from GAM, GBM, GLM, and Maxent models. Results We found that egg ovipositions take place exclusively on the tree species Fraxinus excelsior, preferably exposed to the south, partly shaded, and at medium height (3 m). Our habitat suitability models based on high resolution aerial pictures indicate that egg ovipositions are clustered and accumulate along forest edges and at sites with high forest heterogeneity. Conclusion Our study underlines the high relevance and importance of light deciduous forest structures with environmental dynamics creating the preconditions of specific microhabitat structures for endangered species, such as E. maturna. Our study shows that UAV-captured high precision aerial imagery are well suited to optimally connect two spatial scales, the ecosystem and microhabitat scale.

Purpose The 17 Sustainable Development Goals (SDGs) and their 169 targets pose the most important framework for sustainable development worldwide. However, the contributions of products and companies to the SDGs using social and environmental life cycle assessment (S-LCA; E-LCA) have not been thoroughly addressed in the scientific literature. The purpose of this research is therefore to identify product-related targets, derive suitable indicators and develop a social life cycle impact assessment (S-LCIA) method. Methods To systematically select product-related targets, two questions are developed. The questions ask whether a product (a) has a direct impact on the achievement of the target or (b) if the companies along the life cycle that produce or offer the product have a direct influence on the achievement of the respective target. Suitable indicators are derived and adapted from generally accepted frameworks such as the Global Indicator Framework (GIF-SDG). To develop an S-LCIA method, the targets are translated into conditions beneficial or damaging to the achievement of the target to estimate the socio-economic impact of the product using a scale from +1 to −1. In cases where the targets remain vague, a systematic five-step approach to derive a quantifiable target involving five steps is applied. Results and discussion The main contribution of this paper is to propose a coherent method to measure the contribution of products to the targets. All 17 SDGs and 61 of the 169 targets (36%) were evaluated as product-related. For 57% of the product-related targets, indicators from the GIF-SDGs could at least partly be used after slight adaptations, while for the remaining 43% of the product-related targets, indicators were taken from other frameworks or sources or had to be added. In total, 45 indicators have been identified to be suitable for assessing the potential contribution of products to the 61 targets. To illustrate the systematic five-step approach to quantitatively assess the contribution of products to the targets, five types of contribution functions are presented in detail. Conclusions The presented method allows companies to analyse their impact and that of their products on the targets both within their own company and in the supply chain. As especially the latter is increasingly demanded by supply chain laws in different countries such as France, the Netherlands or the UK, the method fills an important research gap. However, future research to examine the proposed approach, the derived indicators and the impact assessment method is strongly encouraged.

The red blood cell (RBC) pyruvate kinase deficiency (PKD) is the most common recessive congenital defect of glycolytic enzymes associated with non-spherocytic hemolytic anemia. It is a rare hereditary disorder caused by >300 variants in the PKLR gene. This is a retrospective study of 19 patients from different centers from Argentina with confirmed molecular diagnosis of PKD. Clinical follow-up was carried out from birth in most cases. Five consanguineous patients from “gypsy” community, were homozygous for the “PK-Gypsy deletion” (PK-Gd). During the neonatal period they developed anemia with icterus. Transfusion exchange was required in 60%, light therapy in 80%, and RBC transfusion in 80%. During the follow-up iron overload was detected in the 100%, cholecystectomy was indicated in 40%, and splenectomy in 60%. Thirteen cases had 2 missense variants (MS), being the Mediterranean variant (p.Arg486Trp) the more frequent detected (26%).Only 1 patient had a missense-splicing mutation combination. During the neonatal period, 86% had anemia and icterus. Light therapy was required in 78%, transfusion exchange in 21% and RBC transfusion in 64%. During the follow-up iron overload was detected in 57% and splenectomy was indicated in 43%. Transfusions (pre-splenectomy and post-splenectomy) were more required in PK-Gd cases as compared with patients with point mutations (100%/60% vs 71%/29% respectively). Our data indicates a high clinical-therapeutic-molecular heterogeneity in PKD patients with the PK-Gd group presenting the most severe cases.

Arachnoid cysts (AC) occur in different intracranial locations. Management and prognosis depend on the clinical presentation and treatment guidelines do not exist. With this study, we want to demonstrate the clinical variety of arachnoid cysts in children and place a focus on outcome factors in operated cases. This retrospective study of a consecutive single unit series of children, who underwent AC surgery between January 2010 and September 2019, provides demographic, clinical, imaging data, and information about surgical treatment and outcome. Overall, 63 patients (71.4 male) underwent surgery. Mean age was 50 months (0-191). Mean follow-up was 40 months (0-121). Eighty-one percent of patients presented with symptoms/signs of raised ICP. Focal neurological deficits were present in 15.9%, headache in 11.1% of children. Galassi cysts represented the predominant type (30.2%), followed by suprasellar (14.3%), quadrigeminal (12.7%), retrocerebellar, CPA and midline (each 11.1%), and hemispheric cysts (7.9%). Endoscopic and microsurgical fenestrations were performed in 27% and 58.7%, stent or shunt insertion in 6.3%/57.9% of the cases. In 33.3% of the cases one and in 12.7%, a second reintervention became necessary. Reoperation rate was significantly higher in children 1 year (p = 0.003). Cyst volume decreased in 85.7%. Seventy percent of the patients were symptom free, 5% suffered from headache, and 22% from developmental disorders. All focal neurological symptoms resolved. Complication rate and outcome are depending on age and cyst location. Recurrence and revision rates are significantly higher in young infants (p = 0.003). Midline cysts with CCA are associated with developmental disorders.

This study aimed to assess the safety and efficacy of stereotactic radiofrequency ablation (SRFA) in patients with hepatocellular adenomas (HCA).Retrospective analyses of all patients referred for SRFA treatment at our institution between January 2010 and October 2020 revealed 14 patients (10 women; mean age 34.4 [range, 17-73 years]) with 38 HCAs treated through 18 ablation sessions. Ablations were considered successful if a safety margin5 mm was achieved. Demographic, interventional, and outcome data were collected and analyzed. Primary and secondary technical efficacy rates were assessed based on follow-up images consisting of contrast-enhanced CT or MR scans.The mean tumor size was 22 mm (range, 7-75 mm). Overall, 37/38 (97.4%) tumors were successfully ablated at the initial SRFA (primary efficacy rate of 97.4%). The median follow-up duration was 49.6 months. No deaths or adenoma-related complications (hemorrhage or malignant transformation) were observed. Disease-free survival rates at 1, 3, and 5 years from the date of the first SRFA were 100%, 85.8%, and 85.8%, respectively. Two patients developed new distant tumors retreated with consecutive re-ablation. No major complications occurred during any of the 18 ablation sessions.Percutaneous thermal ablation is efficient in the treatment of HCAs and may thus be considered a valid first-line treatment option. In addition, SRFA allows for an effective, minimally invasive treatment of large and multiple hepatic tumors within one session.