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Background/Objectives: Septic shock is a severe condition with high mortality necessitating precise prognostic tools for improved patient outcomes. This study aimed to evaluate the collective predictive value of the Simplified Acute Physiology Score 3 (SAPS-3) and lactate measurements (initial, peak, last, and clearance rates within the first 24 h) in patients with septic shock. Specifically, it sought to determine how these markers enhance predictive accuracy for 28-day mortality beyond SAPS-3 alone. Methods: This retrospective cohort study analyzed data from 66 septic shock patients at two ICUs of Vienna General Hospital (2017–2019). SAPS-3 and lactate levels (initial, peak, last measurement within 24 h, and 24 h clearance) were obtained from electronic health records. Logistic regression models were constructed to identify predictors of 28-day mortality, and receiver operating characteristic (ROC) curves assessed predictive accuracy. Results: Among 66 patients, 36 (55%) died within 28 days. SAPS-3 scores significantly differed between survivors and non-survivors (76 vs. 85 points; p = 0.016). First, last, and peak lactate were significantly higher in non-survivors compared to survivors (all p < 0.001). The combination of SAPS-3 and first lactate produced the highest predictive accuracy (AUC = 80.6%). However, 24 h lactate clearance was not predictive of mortality. Conclusions: Integrating SAPS-3 with lactate measurements, particularly first lactate, improves predictive accuracy for 28-day mortality in septic shock patients. First lactate serves as an early, robust prognostic marker, providing crucial information for clinical decision-making and care prioritization. Further large-scale studies are needed to refine these predictive tools and validate their efficacy in guiding treatment strategies. [ABSTRACT FROM AUTHOR]

Drawing on the nationally representative Census Bureau Household Pulse Survey (N = 443,375), this study examined how pre-pandemic and pandemic-induced vulnerabilities shaped racial inequalities in housing insecurity from August to December 2020. Theorizing the pandemic as a “systemic shock,” this article helps explain how racial inequalities are reproduced both as legacies of long-standing disparities and through widespread, societal moments of disruption. Our results indicated that Black, Hispanic, and Asian households were all significantly more likely to fall behind on housing payments than white households. We found that preexisting racial inequities, including in educational attainment, household income, and homeownership rates, largely explained racial disparities in housing insecurity during COVID-19. However, the pandemic also induced new pathways to racial inequalities. Black and Hispanic households were more likely to lose income and when they lost income, they faced a greater likelihood of experiencing housing insecurity. We conclude by highlighting the importance of theorizing disruptive systemic shocks to understand racial inequalities and discuss findings of both disparities faced by Black and Hispanic households, as well as underrecognized housing insecurity among Asian Americans. [ABSTRACT FROM AUTHOR]

Background: The production of surfactin, an extracellular accumulating lipopeptide produced by various Bacillus species, is a well-known representative of microbial biosurfactant. However, only limited information is available on the correlation between the growth rate of the production strain, such as B. subtilis BMV9, and surfactin production. To understand the correlation between biomass formation over time and surfactin production, the availability of glucose as carbon source was considered as main point. In fed-batch bioreactor processes, the B. subtilis BMV9 was used, a strain well-suited for high cell density fermentation. By adjusting the exponential feeding rates, the growth rate of the surfactin-producing strain, was controlled. Results: Using different growth rates in the range of 0.075 and 0.4 h-1, highest surfactin titres of 36 g/L were reached at 0.25 h-1 with production yields YP/S of 0.21 g/g and YP/X of 0.7 g/g, while growth rates lower than 0.2 h-1 resulted in insufficient and slowed biomass formation as well as surfactin production (YP/S of 0.11 g/g and YP/X of 0.47 g/g for 0.075 h-1). In contrast, feeding rates higher than 0.25 h-1 led to a stimulation of overflow metabolism, resulting in increased acetate formation of up to 3 g/L and an accumulation of glucose due to insufficient conversion, leading to production yields YP/S of 0.15 g/g and YP/X of 0.46 g/g for 0.4 h-1. Conclusions: Overall, the parameter of adjusting exponential feeding rates have an important impact on the B. subtilis productivity in terms of surfactin production in fed-batch bioreactor processes. A growth rate of 0.25 h-1 allowed the highest surfactin production yield, while the total conversion of substrate to biomass remained constant at the different growth rates. [ABSTRACT FROM AUTHOR]

Diffusion-type problems in (nearly) unbounded domains play important roles in various fields of fluid dynamics, biology, and materials science. The aim of this paper is to construct accurate absorbing boundary conditions (ABCs) suitable for classical (local) as well as nonlocal peridynamic (PD) diffusion models. The main focus of the present study is on the PD diffusion formulation. The majority of the PD diffusion models proposed so far are applied to bounded domains only. In this study, we propose an effective way to handle unbounded domains both with PD and classical diffusion models. For the former, we employ a meshfree discretization, whereas for the latter the finite element method (FEM) is employed. The proposed ABCs are time-dependent and Dirichlet-type, making the approach easy to implement in the available models. The performance of the approach, in terms of accuracy and stability, is illustrated by numerical examples in 1D, 2D, and 3D. [ABSTRACT FROM AUTHOR]

The reductive coupling of an N‐heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2‐divinyldiborene, which, although isoelectronic to a 1,3,5‐triene, displays no extended π conjugation because of twisting of the C2B2C2 chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η2‐B2 and η4‐C2B2 fashion, respectively, it undergoes a complex rearrangement to an η4‐1,3‐diborete upon complexation with nickel(0). [ABSTRACT FROM AUTHOR]

The reductive coupling of an N‐heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2‐divinyldiborene, which, although isoelectronic to a 1,3,5‐triene, displays no extended π conjugation because of twisting of the C2B2C2 chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η2‐B2 and η4‐C2B2 fashion, respectively, it undergoes a complex rearrangement to an η4‐1,3‐diborete upon complexation with nickel(0). [ABSTRACT FROM AUTHOR]

Severe thrombocytopenia poses a high risk for bleeding thus representing a relative contraindication for anticoagulation and therefore extracorporeal membrane oxygenation (ECMO). We herein report on a series of immunocompromised patients with severe thrombocytopenia undergoing long‐term ECMO without systemic anticoagulation. We retrospectively identified seven adult patients with anticoagulation withdrawal for ≥3 days (range 5–317) during venovenous ECMO therapy due to thrombocytopenia < 50 G/L treated in a university‐affiliated hospital from January 2013 to April 2017. All ECMO systems used were heparin coated. Overall, 530 ECMO days were observed, 404 (76%) of them without systemic anticoagulation. Platelet count during ECMO treatment was 24 G/L (median, range 1‐138), ECMO duration was 35 days (5‐317), and ECMO was run without any anticoagulation for 20 days (5‐317). Altogether, five clotting events were seen leading to oxygenator exchanges. Bleeding was common including one fatal intracerebral hemorrhage. Altogether, 29 platelet concentrates per patient (7‐207) were administered, which correspond to 0.8 per day (0.6‐1.3). One patient survived ICU and hospital. In patients with thrombocytopenia, ECMO can be run without anticoagulation even for considerably long periods of time. Bleeding remains common, while clotting events seem to be rare. However, prognosis of this patient population undergoing ECMO support seems grim. [ABSTRACT FROM AUTHOR]

In current practice, the day-ahead market-clearing outcomes are not necessarily feasible for distribution networks, i.e., the network constraints might not be satisfied. Hence, the distribution system operator may consider an ex-post re-dispatch mechanism, exploiting potential flexibility of local distributed energy resources including demand response (DR) units. Many DR units have an inherent “rebound effect,” meaning a decrease in power demand (response) must be followed by an increase (rebound) or vice versa, due to their underlying physical properties. A naive re-dispatch mechanism relying on DR units with non-negligible rebound effect may fail, since those units may cause another congestion in the rebound period. We propose a mechanism, which models the rebound effect of DR units using asymmetric block offers—this way, those units offer their flexibility using two subsequent blocks (response and rebound), each one representing the load decrease/increase in a time period. We demonstrate that though linear approximations of optimal power flow (OPF) models as potential re-dispatch mechanisms are more computationally efficient, they can result in a different dispatch of the asymmetric blocks than an exact convex relaxation of an AC-OPF model, and therefore, must be used with caution. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study sought to evaluate the efficacy of various lactate measurements within the first 24 h post-intensive care unit (ICU) admission for predicting 30-day mortality in cardiogenic shock patients. It compared initial lactate levels, 24 h levels, peak levels, and 24 h clearance, alongside the Simplified Acute Physiology Score 3 (SAPS3) score, to enhance early treatment decision-making. Methods: A retrospective analysis of 64 patients assessed the prognostic performance of lactate levels and SAPS3 scores using logistic regression and AUROC calculations. Results: Of the baseline parameters, only the SAPS3 score predicted survival independently. The lactate level after 24 h (LL) was the most accurate predictor of mortality, outperforming initial levels, peak levels, and 24 h-clearance, and showing a significant AUROC. LL greater than 3.1 mmol/L accurately predicted mortality with high specificity and moderate sensitivity. Conclusions: Among lactate measurements for predicting 30-day mortality in cardiogenic shock, the 24 h lactate level was the most effective one, suggesting its superiority for early prognostication over initial or peak levels and lactate clearance. [ABSTRACT FROM AUTHOR]

Abstract: Die Umsetzung von Bis(catecholato)diboran mit N‐heterocyclischen Carbenen (NHCs) lieferte sp2‐sp3‐Diborane, die hochselektiv einen Catechol/Bromid‐Austausch am sp3‐Boratom eingehen. Die Reduktion der erhaltenen 1,1‐Dibromdiboran‐Addukte führte zur reduktiven Kupplung und Isolierung von zweifach NHC‐stabilisierten 1,2‐Diboryldiborenen. Mit diesen Molekülen konnte erstmals eine Delokalisierung von π‐Elektronen über eine nur aus Boratomen bestehende Kette realisiert werden. [ABSTRACT FROM AUTHOR]

Abstract: B(sp2)–B(sp3) diborane species based on bis(catecholato)diboron and N‐heterocyclic carbenes (NHCs) underwent catechol/bromide exchange selectively at the sp3‐hybridized boron atom. The reduction of the resulting 1,1‐dibromodiborane adducts led to reductive coupling and isolation of doubly NHC‐stabilized 1,2‐diboryldiborenes. These compounds are the first examples of molecules exhibiting π‐electron delocalization over an all‐boron chain. [ABSTRACT FROM AUTHOR]

We report two rare instances of an insertion into the strong (ca. 170 kcal mol−1) BN triple bond of iminoboranes. In the first, a silylene inserts into di-tert-butyliminoborane to form an iminosilane. In the second, the highly crowded iminoborane Ter–NB–TMP (TMP = 2,2,6,6-tetramethylpiperidyl, Ter = 2,6-(diphenylmethyl)-4-tert-butylphenyl) can be forced to react with Pip–CC–Pip (Pip = piperidyl) at 60 °C. The reaction product is the apparent result of Pip–CC insertion into the iminoborane BN bond. [ABSTRACT FROM AUTHOR]

The focus of this paper is on application of peridynamics (PD) to propagation of elastic waves in unbounded domains. We construct absorbing boundary conditions (ABCs) derived from a semi-analytical solution of the PD governing equation at the exterior region. This solution is made up of a finite series of plane waves, as fundamental solutions (modes), which satisfy the PD dispersion relations. The modes are adjusted to transmit the energy from the interior region (near field) to the exterior region (far field). The corresponding unknown coefficients of the series are found in terms of the displacement field at a layer of points adjacent to the absorbing boundary. This is accomplished through a collocation procedure at subregions (clouds) around each absorbing point. The proposed ABCs offer appealing advantages, which facilitate their application to PD. They are of Dirichlet-type, hence their implementation is relatively simple as no derivatives of the field variables are required. They are constructed in the time and space domains and thus application of Fourier and Laplace transforms, cumbersome for nonlocal models, is not required. At the discrete level, the modes satisfy the same numerical dispersion relations of the near field, which makes the far-field solution compatible with that of the near field. We scrutinize the performance of the proposed ABCs through several examples. Our investigation shows that the proposed ABCs perform stably in time with an appropriate level of accuracy even in problems characterized by highly-dispersive propagating waves, including crack propagation in semi-unbounded brittle solids. • Development of absorbing boundary conditions for 2D bond-based peridynamics. • Introduction of easy-to-implement, Dirichlet-type absorbing boundary conditions. • Approximation of the far-field solution in consistency with the near-field solution. • Construction of the absorbing boundary conditions in the time and space domains. • Solution of propagating cracks in a half-space. [ABSTRACT FROM AUTHOR]

Purpose: Pump-driven veno-venous extracorporeal CO2-removal (ECCO2-R) increasingly takes root in hypercapnic lung failure to minimize ventilation invasiveness or to avoid intubation. A recently developed device (iLA activve(®), Novalung, Germany) allows effective decarboxylation via a 22 French double lumen cannula. To assess determinants of gas exchange, we prospectively evaluated the performance of ECCO2-R in ten patients receiving iLA activve(®) due to hypercapnic respiratory failure.Methods: Sweep gas flow was increased in steps from 1 to 14 L/min at constant blood flow (phase 1). Similarly, blood flow was gradually increased at constant sweep gas flow (phase 2). At each step gas transfer via the membrane as well as arterial blood gas samples were analyzed.Results: During phase 1, we observed a significant increase in CO2 transfer together with a decrease in PaCO2 levels from a median of 66 mmHg (range 46-85) to 49 (31-65) mmHg from 1 to 14 L/min sweep gas flow (p < 0.0001), while arterial oxygenation deteriorated with high sweep gas flow rates. During phase 2, oxygen transfer significantly increased leading to an increase in PaO2 from 67 (49-87) at 0.5 L/min to 117 (66-305) mmHg at 2.0 L/min (p < 0.0001). Higher blood flows also significantly enhanced decarboxylation (p < 0.0001).Conclusions: Increasing sweep gas flow results in effective CO2-removal, which can be further reinforced by raising blood flow. The clinically relevant oxygenation effect in this setting could broaden the range of indications of the system and help to set up an individually tailored configuration. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Change of treatment policy from closed to open ward settings has been shown to reduce coercive measures. The aim of the current study was to examine the effects of the change from closed to open wards on the frequency of seclusion and forced medication in a hospital-wide setting. Subjects and methods: 2-year, longitudinal observational study with 2838 inpatient cases. Results: On a hospital-wide level, the percentage of patients with at least one seclusion was decreased significantly (χ 2 (1) = 5.8; p = .016), while there was no significant change in forced medication (χ 2(1) = .08; p = .775). The frequency of seclusions and forced medication decreased significantly on newly opened wards, and there were no significant changes regarding seclusion on permanently closed or open wards, while the number of forced medications increased significantly on closed wards. The decrease in seclusions on newly opened wards remained statistically significant after controlling for diagnoses and severity of illness. Discussion: Our results indicate that a reduction of overall seclusion can be successfully attained, and that, in particular, the frequency of seclusion and forced medication on newly opened wards was decreased significantly. These changes were not accompanied by a significant increase in seclusion on other wards. Conclusion: Open ward treatment was successfully implemented and was associated with a significant decrease of coercive measures in our study. It might therefore provide a good care model, strengthening the patient's right to autonomy and leading to a reduction of coercive measures. [Copyright &y& Elsevier]

This paper proposes a computational framework to describe the biodegradation of magnesium (Mg)-based bone implants. It is based on a sequential combination of two models: an electrochemical corrosion model to compute the mass loss of the implant over several weeks combined with a mechanical model to assess its residual mechanical strength. The first model uses a peridynamic (PD) corrosion model to tackle the complex moving boundary of the corroding material in an efficient manner. The results of this corrosion simulation are mapped to a finite element (FE) model by way of a damage variable. Subsequently, the FE model is used for mechanical analysis. To use PD for such a complex problem, we proposed three innovative improvements compared to state-of-the-art PD models: (1) application of an adaptive multi-grid discretization in space and an implicit time-stepping algorithm enabling an efficient simulation of the complex implant geometry over prolonged periods, (2) novel non-local Dirichlet absorbing boundary conditions to truncate the simulation domain in the close neighborhood of the implant of interest without prohibitive losses of accuracy, and (3) selection of suitable non-local kernel functions and parameter calibration on the basis of experimental data by an evolutionary algorithm. We demonstrate that this framework can capture the loss of implant mass due to corrosion for typical alloys such as Mg-5Gd and Mg-10Gd. Moreover, we point out how this framework can be used in the future to predict the declining mechanical strength of bone screws subject to biocorrosion over several weeks. [Display omitted] • Development of a novel framework to model biodegradation of Mg-based implants. • Extension of a peridynamic corrosion model to simulate electrochemical biocorrosion. • Enhancing the numerical performance through a multi-grid approach. • Introduction of a new strategy of calibration for peridynamic corrosion models. • Devising a sequential approach to incorporate a finite element damage analysis. [ABSTRACT FROM AUTHOR]

Efficient and accurate calculation of spatial integrals is of major interest in the numerical implementation of peridynamics (PD). The standard way to perform this calculation is a particle-based approach that discretizes the strong form of the PD governing equation. This approach has rapidly been adopted by the PD community since it offers some advantages. It is computationally cheaper than other available schemes, can conveniently handle material separation, and effectively deals with nonlinear PD models. Nevertheless, PD models are still computationally very expensive compared with those based on the classical continuum mechanics theory, particularly for large-scale problems in three dimensions. This results from the nonlocal nature of the PD theory which leads to interactions of each node of a discretized body with multiple surrounding nodes. Here, we propose a new approach to significantly boost the numerical efficiency of PD models. We propose a discretization scheme that employs a simple collocation procedure and is truly meshfree; i.e., it does not depend on any background integration cells. In contrast to the standard scheme, the proposed scheme requires a much smaller set of neighboring nodes (keeping the same physical length scale) to achieve a specific accuracy and is thus computationally more efficient. Our new scheme is applicable to the case of linear PD models and within neighborhoods where the solution can be approximated by smooth basis functions. Therefore, to fully exploit the advantages of both the standard and the proposed schemes, a hybrid discretization is presented that combines both approaches within an adaptive framework. The high performance of the developed framework is illustrated by several numerical examples, including brittle fracture and corrosion problems in two and three dimensions. [ABSTRACT FROM AUTHOR]

This study compares the subcellular localization and the regulation of expression of the platelet activation markers CD62P and CD63 with CD40 ligand (CD40L) on the surface of washed human platelets. CD40L was expressed upon stimulation with a wide range of platelet activators. However, quantitative flow cytometry demonstrated that, as compared with CD62P and CD63, CD40L expression was low. Upon stimulation with thrombin receptor-activating peptide (TRAP-6), all activation markers were expressed. In contrast, upon stimulation with low concentrations of collagen (1-3 μ g/ml), CD40L, but not the granule proteins (CD62P, CD63), were expressed. Using immunofluorescence microscopy, a cytoplasmic staining was observed for CD40L, and cytoplasmic localization of CD40L was verified by Western blotting of subcellular platelet fractions. The staining of CD40L was different from that of filamentous actin and only little association of CD40L with platelet cytoskeleton was found. Surface expression of CD40L was dependent on internal Ca[sup 2+] stores and protein kinase C, while the mitogen-activated protein kinases (ERK, p38) or tyrosine kinases were not involved. ADP (30 μ M)-induced CD40L expression was not inhibited by aspirin. In contrast, clopidogrel treatment completely abolished ADP-induced expression of CD40L. Finally, the expression level of CD40L was shown to be upregulated by phorbol myristate acetate (PMA) in the promegakaryocytic cell line MEG-01. [ABSTRACT FROM AUTHOR]

Although extracorporeal membrane ventilation offers the possibility for low-frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low-frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low-frequency ventilation on ventilator-free days (VFDs) in patients suffering from ARDS who were treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to the control group (conventional ventilation) or the treatment group (low-frequency ventilation during first 72 h on ECMO: respiratory rate 4–5/min; PEEP 14–16 cm H2O; plateau pressure 23–25 cm H2O, tidal volume: <4 mL/kg). The primary endpoint was VFDs at day 28 after starting ECMO treatment. The major secondary endpoint was ICU mortality, 28-day mortality and 90-day mortality. Results: Twenty-three (52%) patients were successfully weaned from ECMO and were discharged from the intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 of ECMO treatment. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (p = 0.117). Until day 28 of ECMO initiation, patients in the treatment group could be successfully weaned off of the ventilator more often (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036–0.758; p = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; p = 0.227). Conclusions: Low-frequency ventilation is comparable to conventional protective ventilation in patients with ARDS who have been treated with ECMO. However, low-frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS and treated with ECMO therapy. [ABSTRACT FROM AUTHOR]

• LCN2 levels correlate with severity of acute and chronic GvHD following HSCT. • LCN2 is elevated in HSCT patients with adverse outcome and relapse. • LCN2 might therefore be useful as an activity parameter of GvHD after HSCT. Lipocalin-2 (LCN2) is an immunomodulatory protein holding major metabolic and immune functions. It is involved in several inflammatory processes and induced by cytokines of the interleukin-1 family known as contributors to the morbidity in graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). The possible role of LCN2 in predicting outcome and course of illness has never been elucidated in patients undergoing HSCT for hematologic malignancies. We conducted a prospective cohort study including 40 patients following autologous or allogeneic HSCT by collecting plasma samples at seven time points with respect to GVHD, relapse, and outcome. LCN2 levels were significantly increased in acute patients with GVHD compared with autologous and healthy controls (125.7 ng/mL vs. 65.9 and 71.4 ng/mL) and correlated with its severity. Similarly, LCN2 levels were significantly elevated in chronic GHVD compared with autologous and healthy controls (295.0 ng/mL vs. 54.9 and 76.5 ng/mL). Moreover, LCN2 correlated with mortality. The suspected role of LCN2 as a predictive parameter for outcome and prognosis needs to be further investigated. [ABSTRACT FROM AUTHOR]

The article focuses on a study that describe performance of gas exchange by raising concerns related to removal rate and calculation method for content of carbon dioxide (CO2). Topics discussed include overestimation of decarboxylation rate as mentioned by the authors in a study, emphasis on arterial blood gas pressures of patients in study and presents a case of veno-venous extracorporeal membrane oxygenation (ECMO) in a patient.

Peridynamic (PD) models are commonly implemented by exploiting a particle-based method referred to as standard scheme. Compared to numerical methods based on classical theories (e.g., the finite element method), PD models using the meshfree standard scheme are typically computationally more expensive mainly for two reasons. First, the nonlocal nature of PD requires advanced quadrature schemes. Second, non-uniform discretizations of the standard scheme are inaccurate and thus typically avoided. Hence, very fine uniform discretizations are applied in the whole domain even in cases where a fine resolution is per se required only in a small part of it (e.g., close to discontinuities and interfaces). In the present study, a new framework is devised to enhance the computational performance of PD models substantially. It applies the standard scheme only to localized regions where discontinuities and interfaces emerge, and a less demanding quadrature scheme to the rest of the domain. Moreover, it uses a multi-grid approach with a fine grid spacing only in critical regions. Because these regions are identified dynamically over time, our framework is referred to as multi-adaptive. The performance of the proposed approach is examined by means of two real-world problems, the Kalthoff–Winkler experiment and the bio-degradation of a magnesium-based bone implant screw. It is demonstrated that our novel framework can vastly reduce the computational cost (for given accuracy requirements) compared to a simple application of the standard scheme. [ABSTRACT FROM AUTHOR]

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration. [ABSTRACT FROM AUTHOR]

The reactions of carbodiimides with the iron arylborylene complex [Fe=BDur(CO)3(PMe3)] (Dur=2,3,5,6‐Me4C6H) and the iron bis(borylene) complex [Fe{=BDur}{=BN(SiMe3)2}(CO)3] yield a wide variety of temperature‐dependent products, including known FeBNC and novel FeBNB metallacycles, complexes of N‐heterocyclic boracarbene and spiro‐boracarbene ligands and a unique 1,3,2,4‐diazadiborolyl pianostool complex, characterized by NMR spectroscopy and X‐ray crystallography. The product distributions can be rationalized by considering sequences of cycloaddition, metathesis, insertion, and C−H activation pathways mainly governed by sterics. [ABSTRACT FROM AUTHOR]

Acute respiratory failure (ARF) is the main reason for ICU admission following allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal CO2 removal (ECCO2R) can be used as an adjunct to mechanical ventilation in patients with severe hypercapnia but has not been assessed in HSCT recipients. Retrospective analysis of all allogeneic HSCT recipients ≥18 years treated with ECCO2R at two HSCT centers. 11 patients (m:f = 4:7, median age: 45 [IQR: 32‐58] years) were analyzed. Acute leukemia was the underlying hematologic malignancy in all patients. The time from HSCT to ICU admission was 37 [8‐79] months, and 9/11 (82%) suffered from chronic graft‐versus‐host disease (GVHD) with lung involvement. Pneumonia was the most frequent reason for ventilatory decompensation (n = 9). ECCO2R was initiated for severe hypercapnia (PaCO2: 96 [84‐115] mm Hg; pH: 7.13 [7.09‐7.27]) despite aggressive mechanical ventilation (invasive, n = 9; non‐invasive, n = 2). ECCO2R effectively resolved blood gas disturbances in all patients, but only 2/11 (18%) could be weaned off ventilatory support, and one (9%) patient survived hospital discharge. Progressive respiratory and multiorgan dysfunction were the main reasons for treatment failure. ECCO2R was technically feasible but resulted in a low survival rate in our cohort. A better understanding of the prognosis of ARF in patients with chronic GVHD and lung involvement is necessary before its use can be reconsidered in this setting. [ABSTRACT FROM AUTHOR]

Reduction of (CAAC)BBr2(NCS) (CAAC=cyclic alkyl(amino)carbene) in the presence of a Lewis base L yields tricoordinate (CAAC)LB(NCS) borylenes which undergo reversible E/Z‐isomerization. The same reduction in the absence of L yields deep blue, bis(CAAC)‐stabilized, boron‐doped, aromatic thiazolothiazoles resulting from the dimerization of dicoordinate (CAAC)B(NCS) borylene intermediates. [ABSTRACT FROM AUTHOR]

Die Reduktion von (CAAC)BBr2(NCS) (CAAC=cyclisches Alkyl(amino)carben) in der Gegenwart einer Lewis‐Base L liefert dreifach koordinierte (CAAC)LB(NCS)‐Borylene, die eine reversible (E)/(Z)‐Isomerisierung eingehen. Die gleiche Reduktion in Abwesenheit von L führt zu intensiv blauen, bis(CAAC)‐stabilisierten, Bor‐dotierten, aromatischen Thiazolthiazolen, die aus der Dimerisierung zweifach koordinierter (CAAC)B(NCS)‐Borylenintermediate resultieren. [ABSTRACT FROM AUTHOR]

Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr2Cym, in benzene results in the formation of the corresponding diborenes (NHC)2B2Cym2, a change of solvent to THF yields a borylene analogue of the form (NHC)2BCym, stabilised through a boratafulvene/borafulvenium conformation. [ABSTRACT FROM AUTHOR]

Die Reaktion zwischen Aryl‐ und Amino(dihydro)boranen und Dibora[2]ferrocenophan 1 führt zur Bildung von 1,3‐trans‐Dihydrotriboranen durch formale Hydrierung und Insertion eines Borylens in die B=B Doppelbindung. Die Aryltriboran‐Derivate unterliegen einer reversiblen Photoisomerisierung zugunsten eines cis‐1,2‐μ‐H‐3‐Hydrotriborans, während eine Hydridabstraktion zu kationischen Triboranen führt, welche die ersten doppelt basenstabilisierten B3H4+‐Analoga darstellen. [ABSTRACT FROM AUTHOR]

The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B3H4+ analogues. [ABSTRACT FROM AUTHOR]

Boryl, borylene, and base-stabilized borylene complexes of manganese and iron undergo a range of different reactions when treated with isonitriles including single, double, and partial isonitrile insertions into metal−boron bonds, ring formation, isonitrile coupling, and the liberation of new monovalent boron species. Two of the resulting cyclic species have also been found to react selectively with anhydrous HCl to form ring-opened products. The diverse isonitrile-promoted reactivity of transition-metal-boron compounds has been explored computationally. [ABSTRACT FROM AUTHOR]

Some patients with diffuse large B-cell lymphoma (DLBCL) require intensive care unit (ICU) admission prior to or during chemotherapy. We analyzed all unscheduled ICU admissions in 331 consecutive patients (18–93 years) with newly diagnosed DLBCL. Thirty-seven patients (11.2%) required ICU treatment primarily due to hemodynamic (37.8%) or respiratory failure (24.3%). Bulky disease and high IPI score were predictive of ICU admission in the early course. ICU and hospital survival was 75.7% and 70.3%, respectively. Overall survival in ICU patients with newly diagnosed DLBCL was worse compared to non-ICU-patients (40.7% vs. 72.7% at two years). However, survival of high-risk patients (IPI 3–5), continuous complete remission, and disease-free survival did not differ. Post-ICU survival was poor in patients with relapsed/refractory DLBCL (0.1–10 months). Our observations favor unrestricted ICU support in DLBCL patients undergoing first-line therapy. ICU referral of patients with refractory/relapsed disease must be evaluated in the context of the hematologic prognosis. [ABSTRACT FROM AUTHOR]

The reactions of isonitriles with a variety of metalloboryl and metalloborylene species are shown to yield a range of products, none of which display the typical Lewis acid–base reactivity previously observed between such metal complexes and other Lewis bases. Insertions of one, or several, isonitriles into the metal–boron bond give cyclic and spiro compounds with bonding controlled by the electron count at the metal and in the ring. [ABSTRACT FROM AUTHOR]

Prognostic factors and outcomes of cancer patients with acute organ failure receiving chemotherapy (CT) in the intensive care unit (ICU) are still incompletely described. We therefore retrospectively studied all patients who received CT in any ICU of our institution between October 2006 and November 2013. Fifty-six patients with hematologic ( n = 49; 87.5 %) or solid ( n = 7; 12.5 %) malignancies, of which 20 (36 %) were diagnosed in the ICU, were analyzed [m/f ratio, 33:23; median age, 47 years (IQR 32 to 62); Charlson Comorbidity Index (CCI), 3 (2 to 5); Simplified Acute Physiology Score II (SAPS II), 50 (39 to 61)]. The main reasons for admission were acute respiratory failure, acute kidney failure, and septic shock. Mechanical ventilation and vasopressors were employed in 34 patients (61 %) respectively, hemofiltration in 22 (39 %), and extracorporeal life support in 7 (13 %). Twenty-seven patients (48 %) received their first CT in the ICU. Intention of therapy was cure in 46 patients (82 %). Tumor lysis syndrome (TLS) developed in 20 patients (36 %). ICU and hospital survival was 75 and 59 %. Hospital survivors were significantly younger; had lower CCI, SAPS II, and TLS risk scores; presented less often with septic shock; were less likely to develop TLS; and received vasopressors, hemofiltration, and thrombocyte transfusions in lower proportions. After discharge, 88 % continued CT and 69 % of 1-year survivors were in complete remission. Probability of 1- and 2-year survival was 41 and 38 %, respectively. Conclusively, administration of CT in selected ICU cancer patients was feasible and associated with considerable long-term survival as well as long-term disease-free survival. [ABSTRACT FROM AUTHOR]