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Martina Veith,1 Julia Tüffers,1 Erika Peychev,1 Andreas Klemmer,1 Viktor Kotke,1 Sabina Janciauskiene,2 Susanne Wilhelm,1 Robert Bals,3 Andreas Rembert Koczulla,4 Claus Franz Vogelmeier,1 Timm Greulich1 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Member of the German Center for Lung Research, Marburg, Germany; 2Clinic for Pneumology, German Center for Lung Research (DZL), Medical University Hannover, Hannover, Germany; 3Department of Internal Medicine V, Pulmonology, Allergology, Respiratory and Intensive Care Medicine, Saarland Hospital, Homburg/Saar, Germany; 4Institute for Pulmonary Rehabilitation Research, Schoen Klinik Berchtesgadener Land, Teaching Hospital of Philipps-University of Marburg, Marburg, GermanyCorrespondence: Martina VeithDepartment of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Member of the German Center for Lung Research, Marburg, GermanyTel +4964215864723Fax +496421586370Email veithm@staff.uni-marburg.dePurpose: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition characterized by low circulating levels of alpha-1antitrypsin (AAT). While the association between AATD and COPD/emphysema is undisputed, the association between AATD and asthma or bronchiectasis is still a matter of debate.Aims and Objectives: Our study aimed to investigate the distribution of AAT genotypes between patients with COPD/emphysema, asthma and bronchiectasis. To back up the diagnostic labels, we described symptoms associated with the diagnosis.Methods: Between September 2003 and March 2020, 29,465 testing kits (AlphaKit®) were analyzed in the AAT laboratory, University of Marburg, Germany. The diagnosis of AATD has been made based on the measurements of AAT serum levels, followed by genotyping, phenotyping or whole gene sequencing depending on the availability and/or the need for more detailed interpretation of the results. The respiratory symptoms were recorded as well.Results: Regarding the distribution of the wild type allele M and the most frequent mutations S (E264V) and Z (E342K), no significant differences could be found between COPD/emphysema [Pi*MM (58.24%); Pi*SZ (2.49%); Pi*ZZ (9.12%)] and bronchiectasis [Pi*MM (59.30%) Pi*SZ (2.81%); Pi*ZZ (7.02%)]. When COPD/emphysema and bronchiectasis were recorded in the same patient, the rate of Pi* ZZ (14.78%) mutations was even higher. Asthma patients exhibited significantly less deficient genotypes [Pi*MM (54.81%); Pi*SZ (2%); Pi*ZZ (2.77%)] than two other groups. Associated respiratory symptoms confirmed the diagnosis.Conclusion: COPD/emphysema and bronchiectasis, but not asthma patients, exhibit higher frequency of AATD genotypes. Our data suggest that AATD testing should be offered to patients with COPD/emphysema and bronchiectasis.Keywords: SERPINA1, alpha-1-antitrypsin deficiency, bronchiectasis, asthma, diagnosis

Agriş and Almas Rivers are tributaries of the Someș River from Salaj County. Both rivers originate from the North slope of Meseș Montain and flows into the Someș River, near the Jibou town. Both are rivers with a relatively natural state, less affected by anthropogenic factors, exceptions are endangered areas where were built longitudinal dams for flood protection. So far, on these rivers there were no ichthyological research conducted. Based on the collected material we performed a complex comparative evaluation of ichtiocenosis of this two rivers and due to their considerable value, we proposed the establishment of a protected area encompassing the entire basin of these rivers.

The title compound, C18H21N3O3, was prepared from 1,3,5-benzenetricarbonyl trichloride and cyclopropylamine. Its crystal structure was solved in the monoclinic space group P21/c. In the crystal, the three amide groups of the molecule are inclined at angles of 26.5 (1), 36.9 (1) and 37.8 (1)° with respect to the plane of the benzene ring. The molecules are linked by N—H...O hydrogen bonds, forming two-dimensional supramolecular aggregates that extend parallel to the crystallographic ab plane and are further connected by C—H...O contacts. As a result of the supramolecular interactions, a propeller-like conformation of the title molecule can be observed.

In the crystal structure of the title compound, C26H36N2O4, the tripodal molecule exists in a conformation in which the substituents attached to the central arene ring are arranged in an alternating order above and below the ring plane. The heterocyclic unit is inclined at an angle of 79.6 (1)° with respect to the plane of the benzene ring. In the crystal, the molecules are connected via N—H...O bonds, forming infinite supramolecular strands. Interstrand association involves weak C—H...O and C—H...π interactions, with the pyridine ring acting as an acceptor in the latter case.

Eating habits are among the strongest drivers of negative environmental impact. Public procurement has been suggested as an efficient lever to catalyze changes within the food system. This study examines alternative purchase processes that may decrease the carbon footprint of publicly procured food through a case study of a municipality in the Northern part of Sweden. The GHG emissions associated with the current food service in the case study were 2.2 kg CO2e per kg food and must be reduced by 40.9% by 2030 to comply with the Paris Agreement; 76% of the emissions derive from food of animal origin (44% from unprocessed red meat). Three alternative diet scenarios, “zero red meat,” “−50% red meat,” and “flexitarian free from red meat,” were explored. Only 6% of the total purchased food kilograms were altered, yet the cutback of meat caused GHG emissions reductions turned out to be as high as 44%. The Swedish Law on Public Procurement, deficient infrastructure, unsustainable food culture, and local politicians' reluctance to change were mentioned as the main obstacles to materializing necessary changes in the food procurement system. The respondents also pointed out essential policy changes at the national and municipal levels.

Remaining useful life prediction models are a central aspect of developing modern and capable prognostics and health management systems. Recently, such models are increasingly data-driven and based on various machine learning techniques, in particular deep neural networks. Such models are notoriously “data hungry”, i.e., to get adequate performance of such models, a substantial amount of diverse training data is needed. However, in several domains in which one would like to deploy data-driven remaining useful life models, there is a lack of data or data are distributed among several actors. Often these actors, for various reasons, cannot share data among themselves. In this paper a method for collaborative training of remaining useful life models based on federated learning is presented. In this setting, actors do not need to share locally held secret data, only model updates. Model updates are aggregated by a central server, and subsequently sent back to each of the clients, until convergence. There are numerous strategies for aggregating clients’ model updates and in this paper two strategies will be explored: 1) federated averaging and 2) federated learning with personalization layers. Federated averaging is the common baseline federated learning strategy where the clients’ models are averaged by the central server to update the global model. Federated averaging has been shown to have a limited ability to deal with non-identically and independently distributed data. To mitigate this problem, federated learning with personalization layers, a strategy similar to federated averaging but where each client is allowed to append custom layers to their local model, is explored. The two federated learning strategies will be evaluated on two datasets: 1) run-to-failure trajectories from power cycling of silicon-carbide metal-oxide semiconductor field-effect transistors, and 2) C-MAPSS, a well-known simulated dataset of turbofan jet engines. Two neural network model architectures commonly used in remaining useful life prediction, long short-term memory with multi-layer perceptron feature extractors, and convolutional gated recurrent unit, will be used for the evaluation. It is shown that similar or better performance is achieved when using federated learning compared to when the model is only trained on local data.

Abstract The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation triggers a cascade of proteolytic events initiated by LP specific enzymes called MASPs (for Mannan-binding lectin Associated Serine Proteases). Elevated serum and brain levels of MASP-2, the effector enzyme of the LP, were previously reported to be associated with the severity of tissue injury and poor outcomes in patients with TBI. To evaluate the therapeutic potential of LP inhibition in TBI, we first conducted a pilot study testing the effect of an inhibitory MASP-2 antibody (α-MASP-2), administered systemically at 4 and 24 h post-TBI in a mouse model of controlled cortical impact (CCI). Treatment with α-MASP-2 reduced sensorimotor and cognitive deficits for up to 5 weeks post-TBI. As previous studies by others postulated a critical role of MASP-1 in LP activation, we conducted an additional study that also assessed treatment with an inhibitory MASP-1 antibody (α-MASP-1). A total of 78 mice were treated intraperitoneally with either α-MASP-2, or α-MASP-1, or an isotype control antibody 4 h and 24 h after TBI or sham injury. An amelioration of the cognitive deficits assessed by Barnes Maze, prespecified as the primary study endpoint, was exclusively observed in the α-MASP-2-treated group. The behavioral data were paralleled by a reduction of the lesion size when evaluated histologically and by reduced systemic LP activity. Our data suggest that inhibition of the LP effector enzyme MASP-2 is a promising treatment strategy to limit neurological deficits and tissue loss following TBI. Our work has translational value because a MASP-2 antibody has already completed multiple late-stage clinical trials in other indications and we used a clinically relevant treatment protocol testing the therapeutic mechanism of MASP-2 inhibition in TBI.

Abstract Alterations in gut microbiota composition are suggested to contribute to cardiometabolic diseases, in part by producing bioactive molecules. Some of the metabolites are produced by very low abundant bacterial taxa, which largely have been neglected due to limits of detection. However, the concentration of microbially produced metabolites from these taxa can still reach high levels and have substantial impact on host physiology. To explore this concept, we focused on the generation of secondary bile acids by 7α-dehydroxylating bacteria and demonstrated that addition of a very low abundant bacteria to a community can change the metabolic output dramatically. We show that Clostridium scindens converts cholic acid into the secondary bile acid deoxycholic acid (DCA) very efficiently even though the abundance of C. scindens is low, but still detectable by digital droplet PCR. We also show that colonization of germ-free female mice with a community containing C. scindens induces DCA production and affects host metabolism. Finally, we show that DCA correlates with impaired glucose metabolism and a worsened lipid profile in individuals with type 2 diabetes, which implies that this metabolic pathway may contribute to the development of cardiometabolic disease.

In the crystal of the title compound, C18H14O10·2H2O, the arene rings of the biphenyl moiety are tilted at an angle of 24.3 (1)°, while the planes passing through the carboxyl groups are rotated at angles of 8.6 (1) and 7.7 (1)° out of the plane of the benzene ring to which they are attached. The crystal structure is essentially stabilized by O—H...O bonds. Here, the carboxyl groups of neighbouring host molecules are connected by cyclic R22(8) synthons, leading to the formation of a three-dimensional network. The water molecules in turn form helical supramolecular strands running in the direction of the crystallographic c-axis (chain-like water clusters). The second H atom of each water molecule provides a link to a methoxy O atom of the host molecule. A Hirshfeld surface analysis was performed to quantify the contributions of the different intermolecular interactions, indicating that the most important contributions to the crystal packing are from H...O/O...H (37.0%), H...H (26.3%), H...C/C...H (18.5%) and C...O/O...C (9.5%) interactions.

Summary: Background: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. Methods: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. Findings: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. Interpretation: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. Funding: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.