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Background: Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI. Methods: All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512 mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc. Results: Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3–39.3%] vs. 15.4% [11.9–18.7%], hazard ratio 2.5 [1.9–3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups. Conclusions: RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment. [ABSTRACT FROM AUTHOR]

Radial artery occlusion (RAO) is a relatively common but benign complication following transradial endovascular approaches. Radial artery thrombectomy offers a potential strategy for re-access. Transradial access in the occluded vessel has been described as safe and feasible in recent literature; however, the step-by-step technical details have not been defined. This illustrative case highlights the technique developed at this institution, which has been performed in 7 consecutive patients. A middle-aged woman underwent initial diagnostic cerebral angiogram and balloon-occlusion test for tumor resection planning. Subsequently, the patient returned to for tumor embolization and was found to have RAO. Radial artery mechanical thrombectomy was performed, and this access was safely used for the embolization procedure. This report provides a technical description with illustrations for this approach in the setting of an acute occlusion following prior radial artery catheterizations. Recanalization of an acutely occluded radial artery is feasible and safe in our institutional experience. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of mortality and disability, with cerebellar strokes posing severe complications such as herniation and brainstem compression. Edaravone, a radical scavenger known for reducing oxidative stress, has shown neuroprotective effects in cerebral strokes, but its impact on cerebellar strokes remains unclear. This study investigates Edaravone’s protective properties in organotypic slice cultures of rat cerebellum and hippocampus, employing an oxygen-glucose deprivation (OGD) model to simulate ischemic stroke. The hippocampus served as comparative structure due to its high hypoxia sensitivity. Our results confirmed effective hypoxic induction with increases in HIF-1α and HIF-2α expression. Edaravone significantly reduced lactate dehydrogenase (LDH) levels, indicating diminished cellular damage, with cerebellar tissues showing greater vulnerability. Additionally, Edaravone reduced reactive oxygen species (ROS) in both tissues, though its efficacy may be limited by higher oxidative stress in cerebellar cultures. Seahorse XF analysis revealed that Edaravone preserved mitochondrial respiration and tissue integrity in cerebellar and hippocampal slice cultures. However, Edaravone was more effective in preserving mitochondrial respiration in hippocampal slices, suggesting that OGD-induced damage is more severe in cerebellar tissue. In conclusion, Edaravone demonstrates significant cell protective effects in both cerebellar and hippocampal tissues under OGD conditions, preserving tissue integrity and enhancing mitochondrial function in a tissue-dependent manner. These findings suggest Edaravone as a promising therapeutic candidate for cerebellar stroke. Further in vivo studies are required to assess its full clinical potential. [ABSTRACT FROM AUTHOR]

Purpose: The Marburg Ion-Beam Therapy Center (MIT) is one of two particle therapy centers in Germany that enables the treatment of patients with both protons and carbon ions. The facility was build by Siemens Healthineers and is one of only two centers worldwide built by Siemens (Marburg, Germany and Shanghai, China). The present report provides an overview of technical and clinical operations as well as research activities at MIT. Methods: The MIT was completed in 2011 and uses a synchrotron for accelerating protons and carbon ions up to energies of 250 MeV/u and 430 MeV/u respectively. Three treatment rooms with a fixed horizontal beam-line and one room with a 45 degree beam angle are available. Results: Since the start of clinical operations in 2015, around 2.500 patients have been treated at MIT, about 40% with carbon ions and 60% with protons. Currently around 400 patients are treated each year. The majority of the patients suffered from benign and malign CNS tumors (around 40%) followed by head and neck tumors (around 23%). MIT is actively involved in clinical studies with its patients. In addition to clinical operations, there is active research at MIT in the fields of radiation biology and medical physics. The focus is on translational research to improve the treatment of H & N carcinomas and lung cancer (NSCLC). Moreover, intensive work is being carried out on the technical implementation of FLASH irradiation for research purposes. Conclusion: The MIT is one of two centers worldwide that were built by Siemens Healtineers and has been successfully in clinical operation since 2015. The service provided by Siemens is guaranteed until 2030, the future after 2030 is currently under discussion. [ABSTRACT FROM AUTHOR]

For reliable pest suppression, benefits of habitat management for natural enemies of agricultural pests need to be consistent over time. Unfortunately, most research projects allow only for one or two years of data collection. Here, we present a five-year study on effects of fungicide reduction and altered plant architecture on arthropod abundances and natural pest control in an experimental vineyard. The vineyard rows were divided into eight groups, half of which were trained in vertical shoot position ("trellis system") and the other half as semi-minimal pruned hedge ("minimal pruning"). Every row was divided in three sections receiving three different plant protection intensities, respectively, with fungicides certified for organic viticulture. In each year we sampled arthropods from the grapevine canopy by standardized leaf collection and beat-sheet sampling, and exposed baits of a major grapevine pest (Lobesia botrana) to assess natural pest control. Arthropods, in particular predators, benefited from reduced fungicide sprayings and in turn promoted natural pest control. In contrast, effects of minimal pruning were less strong, and restricted to the leaf mesofauna, earwigs and leafhoppers. Across the five study years with their variable weather conditions, we conclude that the advantages of reduced fungicide sprayings in fungus-resistant varieties are consistent over time. [ABSTRACT FROM AUTHOR]

Background: Cardiohepatic syndrome (CHS) has been identified as an important but underrecognized survival predictor in multiple cardiovascular disease entities. The objectives of this study were to evaluate the prevalence and prognostic value of CHS in patients undergoing TAVR for severe aortic stenosis (AS). Methods: The study included patients with available laboratory parameters of hepatic function who underwent TAVR from July 2013 until December 2019 at our center. CHS was defined as an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal (bilirubin, alkaline phosphatase, and gamma glutamyl transferase). Study endpoints were three-year survival, technical and device failure (VARC 3), as well as New York Heart Association (NYHA) functional class at follow-up. Results: Among a total of 953 analyzed patients (47.6% females, median age 80.0 [76.0–85.0] years) CHS was present in 212 patients (22.4%). In patients with vs. without CHS, rates of technical (6.1% vs. 8.4%, p = 0.29) and device failure (18.9% vs. 17.3%, p = 0.59) were comparable. NYHA functional class at baseline and follow-up was more severe in patients with CHS. Nevertheless, heart failure symptoms improved from baseline to follow-up irrespective of hepatic function. Three-year survival rates were significantly lower in patients with CHS (49.4 vs. 65.4%, p < 0.001). The predictive value of CHS persisted after adjustment in a multivariable analysis (hazard ratio 1.58, p < 0.01). Conclusion: In patients undergoing TAVR, CHS is prevalent in 22% of patients and is associated with increased postinterventional mortality. Thus, CHS should be included in the decision-making process within the TAVR heart team. Cardiohepatic syndrome (CHS) as defined by an elevation of at least two of three laboratory cholestasis parameters above the upper limit of normal was prevalent in 22% of patients undergoing TAVR for severe AS. The presence of CHS was associated with more severe heart failure symptoms and worse three-year survival. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) experiments utilizing parahydrogen-induced polarization (PHIP) were performed to elucidate the PHIP activity of the synthetic 236 kDa biopolymer poly-γ-(4-propargyloxy)-benzyl-L-glutamate) (PPOBLG). The homopolypeptide was successfully hyperpolarized and the enhanced signals were detected in 11.7 T solution NMR as a function of the PPOBLG concentration. The hydrogenation with parahydrogen caused signal enhancements of 800 and more for the vinyl protons of the side chain at low substrate concentration. As a result of this high enhancement factor, even at 13 nM of PPOBLG, a single scan 1H-NMR detection of the hyperpolarized protons was possible, owing to the combination of hyperpolarization and density of PHIP active sites. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse the predictive value of CTA-determined tricuspid annular dilatation (TAD) on the persistence of tricuspid regurgitation (TR) in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) and concomitant at least moderate TR. Methods and results: 288 consecutive patients treated with TAVR due to severe AS and concomitant at least moderate TR at baseline were included in the analysis. As cutoff for TAD, the median value of the CTA-determined, to the body surface area-normalized tricuspid annulus diameter (25.2 mm/m2) was used. TAD had no impact on procedural characteristics or outcomes, including procedural death and technical or device failure according to the Valve Academic Research Consortium 3 criteria. However, the primary outcome of the study—TR persistence after TAVR was significantly more frequent in patients with compared to patients without TAD (odds ratio 2.60, 95% confidence interval 1.33–5.16, p < 0.01). Multivariable logistic regression analysis, adjusting for clinical and echocardiographic baseline characteristics, which are known to influence aetiology or severity of TR, confirmed TAD as an independent predictor of TR persistence after TAVR (adjusted odds ratio 2.30, 95% confidence interval 1.20–4.46, p = 0.01). Moreover, 2 year all-cause mortality was significantly higher in patients with persistence or without change of TR compared to patients with TR improvement (log-rank p < 0.01). Conclusion: In patients undergoing TAVR for severe AS and concomitant at least moderate TR at baseline, TAD is a predictor of TR persistence, which is associated with increased 2-year all-cause mortality. [ABSTRACT FROM AUTHOR]

Octreotide, a somatostatin analogue, has shown its efficacy for the diagnostics and treatment of various types of cancer, i.e., in octreotide scan, as radio-marker after labelling with a radiopharmaceutical. To avoid toxicity of radio-labeling, octreotide-based assays can be implemented into magnetic resonance techniques, such as MRI and NMR. Here we used a Parahydrogen-Induced Polarization (PHIP) approach as a cheap, fast and straightforward method. Introduction of l-propargyl tyrosine as a PHIP marker at different positions of octreotide by manual Solid-Phase Peptide Synthesis (SPPS) led to up to 2000-fold proton signal enhancement (SE). Cell binding studies confirmed that all octreotide variants retained strong binding affinity to the surface of human-derived cancer cells expressing somatostatin receptor 2. The hydrogenation reactions were successfully performed in methanol and under physiologically compatible mixtures of water with methanol or ethanol. The presented results open up new application areas of biochemical and pharmacological studies with octreotide. [ABSTRACT FROM AUTHOR]

The close interaction between the enteric nervous system, microbiome, and brain in vertebrates is an emerging topic of recent studies. Different species such as rat, mouse, and human are currently being used for this purpose, among others. The transferability of protocols for tissue isolation and sample collection is not always straightforward. Thus, the present work presents a new protocol for isolation and sample collection of rat myenteric plexus cells for in vivo as well as in vitro studies. With the methods and chemicals described in detail, a wide variety of investigations can be performed with regard to normal physiological as well as pathological processes in the postnatal developing enteric nervous system. The fast and efficient preparation of the intestine as the first step is particularly important. We have developed and described a LIENS chamber to obtain optimal tissue quality during intestinal freezing. Cryosections of the flat, snap-frozen intestine can then be prepared for histological examination of the various wall layers of the intestine, e.g. by immunohistochemistry. In addition, these cryosections are suitable for the preparation of defined regions, as shown here using the ganglia of the mesenteric plexus. This specific tissue was obtained by laser microdissection, making the presented methodology also suitable for subsequent analyses that require high quality (specificity) of the samples. Furthermore, we present here a fully modernized protocol for the cultivation of myenteric neurons from the rat intestine, which is suitable for a variety of in vitro studies. [ABSTRACT FROM AUTHOR]

Autophagy of damaged mitochondria, called mitophagy, is an important organelle quality control process involved in the pathogenesis of inflammation, cancer, aging, and age-associated diseases. Many of these disorders are associated with altered expression of the inner mitochondrial membrane (IMM) protein Prohibitin 1. The mechanisms whereby dysfunction occurring internally at the IMM and matrix activate events at the outer mitochondrial membrane (OMM) to induce mitophagy are not fully elucidated. Using the gastrointestinal epithelium as a model system highly susceptible to autophagy inhibition, we reveal a specific role of Prohibitin-induced mitophagy in maintaining intestinal homeostasis. We demonstrate that Prohibitin 1 induces mitophagy in response to increased mitochondrial reactive oxygen species (ROS) through binding to mitophagy receptor Nix/Bnip3L and independently of Parkin. Prohibitin 1 is required for ROS-induced Nix localization to mitochondria and maintaining homeostasis of epithelial cells highly susceptible to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: The study objective was to characterize different groups of low-flow low-gradient (LFLG) aortic stenosis (AS) and determine short-term outcomes and long-term mortality according to Valve Academic Research Consortium-3 (VARC-3) endpoint definitions. Background: Characteristics and outcomes of patients with LFLG AS undergoing transcatheter aortic valve implantation (TAVI) are poorly understood. Methods: All patients undergoing TAVI at our center between 2013 and 2019 were screened. Patients were divided into three groups according to mean pressure gradient (dPmean), ejection fraction (LVEF), and stroke volume index (SVi): high gradient (HG) AS (dPmean ≥ 40 mmHg), classical LFLG (cLFLG) AS (dPmean < 40 mmHg, LVEF < 50%), and paradoxical LFLG (pLFLG) AS (dPmean < 40 mmHg, LVEF ≥ 50%, SVi ≤ 35 ml/m2). Results: We included 1776 patients (956 HG, 447 cLFLG, and 373 pLFLG patients). Most baseline characteristics differed significantly. Median Society of Thoracic Surgeons (STS) score was highest in cLFLG, followed by pLFLG and HG patients (5.0, 3.9 and 3.0, respectively, p < 0.01). Compared to HG patients, odds ratios for the short-term VARC-3 composite endpoints, technical failure (cLFLG, 0.76 [95% confidence interval, 0.40–1.36], pLFLG, 1.37 [0.79–2.31]) and device failure (cLFLG, 1.06 [0.74–1.49], pLFLG, 0.97 [0.66–1.41]) were similar, without relevant differences within LFLG patients. NYHA classes improved equally in all groups. Compared to HG, LFLG patients had a higher 3-year all-cause mortality (STS score-adjusted hazard ratios, cLFLG 2.16 [1.77–2.64], pLFLG 1.53 [1.22–193]), as well as cardiovascular mortality (cLFLG, 2.88 [2.15–3.84], pLFLG, 2.08 [1.50–2.87]). Conclusions: While 3-year mortality remains high after TAVI in LFLG compared to HG patients, symptoms improve in all subsets after TAVI. [ABSTRACT FROM AUTHOR]

Background: Expedited or delayed surgery for colon cancer without appropriate work-up increases mortality risk. We sought to identify what patient, social, and hospital factors were associated with timely, guideline-adherent work-up for colon cancer. Methods: Retrospective analysis of 19,046 patients in the Surveillance, Epidemiology, and End Results (SEER) database linked with Medicare administrative claims who underwent elective surgery for colon cancer between 2010 and 2015 was performed. Primary outcome was receipt of complete preoperative work-up (colonoscopy, imaging, tumor marker evaluation) and timely surgery within 60 days of diagnosis. Patients were stratified into four groups: (1) adherent; (2) early surgery (< 30 days) with incomplete work-up; (3) surgery between 30 and 60 days with incomplete work-up; and (4) late surgery (> 60 days) with/without work-up. Characteristics were compared and multinomial logistic regression was performed. Results: Overall, 46.2% of patients received adherent care, 33.1% had early surgery and inadequate work-up, 10.3% had appropriately timed surgery but incomplete work-up, and 10.4% underwent late surgery. Multivariable analysis demonstrated that older, female, Black, and unmarried patients as well as patients living in areas with higher rates of poverty were more likely to receive non-adherent care. A greater proportion of patients at teaching hospitals received complete work-up (57.6% vs. 49.5%) but also underwent late surgery (12.4% vs. 8.6%) compared with non-teaching hospitals. Conclusions: Patient, societal, and hospital factors impact whether patients receive guideline-adherent colon cancer care. Interventions are needed to improve access to timely and guideline-adherent cancer care as a possible mechanism to combat surgical disparities. [ABSTRACT FROM AUTHOR]

Parahydrogen-induced polarization is a hyperpolarization method for enhancing nuclear magnetic resonance signals by chemical reactions/interactions involving the para spin isomer of hydrogen gas. This method has allowed for biomolecules to be hyperpolarized to such a level that they can be used for real time in vivo metabolic imaging. One particularly promising example is fumarate, which can be rapidly and efficiently hyperpolarized at low cost by hydrogenating an acetylene dicarboxylate precursor molecule using parahydrogen. The reaction is relatively slow compared to the timescale on which the hyperpolarization relaxes back to thermal equilibrium, and an undesirable 2nd hydrogenation step can convert the fumarate into succinate. To date, the hydrogenation chemistry has not been thoroughly investigated, so previous work has been inconsistent in the chosen reaction conditions in the search for ever-higher reaction rate and yield. In this work we investigate the solution preparation protocols and the reaction conditions on the rate and yield of fumarate formation. We report conditions to reproducibly yield over 100 mM fumarate on a short timescale, and discuss aspects of the protocol that hinder the formation of fumarate or lead to irreproducible results. We also provide experimental procedures and recommendations for performing reproducible kinetics experiments in which hydrogen gas is repeatedly bubbled into an aqueous solution, overcoming challenges related to the viscosity and surface tension of the water. [ABSTRACT FROM AUTHOR]

Our study investigated the feasibility to measure pressure profiles inside the inflation balloon during direct implantation of Edwards Sapien 3 ultra-prostheses using an additional syringe with a digital pressure read-out. Pressure profiles of 15 patients for 26 mm valve size were analyzed. Uniform patterns were found for 5 patients similar to those of previously acquired in vitro curves. 10 patients showed strikingly different pressure profiles compared to the above-mentioned group, marked by an earlier pressure increase, single or multiple pressure drops or higher overall pressure. Measuring the percentage of under-expansion of the prostheses, using calibrated angiographic projections revealed a significant difference between both groups. Our data raises the hypothesis that the acquisition of pressure profiles might help to better understand not only the implantation procedure itself but also the highly individual patient-device interaction, offering new information and a new perspective on optimization of TAVR implantation in the future. [ABSTRACT FROM AUTHOR]

Background: Treatment with extracorporeal life support (ECLS) in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) fell short of improving myocardial recovery measured by 30 day ejection fraction in the ECLS-SHOCK trial. However, to date, no data regarding impact of ECLS on long-term outcomes exist. Methods: In this randomized, controlled, prospective, open-label trial, 42 patients with CS complicating AMI were randomly assigned to ECLS (ECLS group, n = 21) or no ECLS (control group, n = 21). The primary endpoint was left ventricular ejection fraction (LVEF) after 30 days. Secondary endpoints included mortality and neurological outcome after 12 months. Evaluation of neurological outcome used the modified Rankin Scale. Results: The 12-month all-cause mortality was 19% in the ECLS group versus 38% in the control group (p = 0.31). Only one patient (control group) died after the initial 30 days. Three patients underwent elective percutaneous coronary intervention (PCI) during follow-up (one in the control and two in the ECLS group). Favorable neurological outcome (modified Rankin Score ≤ 2) was seen in 61.9% of patients in the ECLS group versus 57.1% in the control group (p = 1). Conclusion: This pilot study showed that randomized studies with ECLS in CS patients are feasible and safe. Small numbers of included patients impede meaningful conclusions about mortality and neurological outcome. Our findings of numerical differences in mortality and survival with severe neurological impairment give an urgent call for larger multi-centric randomized trials assessing the endpoint of all-cause mortality but also considering the effects on neurological outcome measures. [ABSTRACT FROM AUTHOR]

Deactivation processes of photoexcited (λex = 580 nm) phycocyanobilin (PCB) in methanol were investigated by means of UV/Vis and mid-IR femtosecond (fs) transient absorption (TA) as well as static fluorescence spectroscopy, supported by density-functional-theory calculations of three relevant ground state conformers, PCBA, PCBB and PCBC, their relative electronic state energies and normal mode vibrational analysis. UV/Vis fs-TA reveals time constants of 2.0, 18 and 67 ps, describing decay of PCBB*, of PCBA* and thermal re-equilibration of PCBA, PCBB and PCBC, respectively, in line with the model by Dietzek et al. (Chem Phys Lett 515:163, 2011) and predecessors. Significant substantiation and extension of this model is achieved first via mid-IR fs-TA, i.e. identification of molecular structures and their dynamics, with time constants of 2.6, 21 and 40 ps, respectively. Second, transient IR continuum absorption (CA) is observed in the region above 1755 cm−1 (CA1) and between 1550 and 1450 cm−1 (CA2), indicative for the IR absorption of highly polarizable protons in hydrogen bonding networks (X–H...Y). This allows to characterize chromophore protonation/deprotonation processes, associated with the electronic and structural dynamics, on a molecular level. The PCB photocycle is suggested to be closed via a long living (> 1 ns), PCBC-like (i.e. deprotonated), fluorescent species. [ABSTRACT FROM AUTHOR]

A key predictor of morbidity and mortality for patients with a bloodstream infection is time to appropriate antimicrobial therapy. Accelerating antimicrobial susceptibility testing from positive blood cultures is therefore key to improving patient outcomes, yet traditional laboratory approaches can require 2–4 days for actionable results. The eQUANT—a novel instrument utilizing electrical biosensors—produces a standardized inoculum equivalent to a 0.5 McFarland directly from positive blood cultures. This proof-of-concept study demonstrates that eQUANT inocula prepared from clinically significant species of Enterobacterales were comparable to 0.5 McF inocula generated from bacterial colonies in both CFU/ml concentration and performance in antimicrobial susceptibility testing, with ≥ 95% essential and categorical agreement for VITEK2 and disk diffusion. The eQUANT, combined with a rapid, direct from positive blood culture identification technique, can allow the clinical laboratory to begin antimicrobial susceptibility testing using a standardized inoculum approximately 2–3 h after a blood culture flags positive. This has the potential to improve clinical practice by accelerating conventional antimicrobial susceptibility testing and the resulting targeted antibiotic therapy. [ABSTRACT FROM AUTHOR]

The identification of energetic materials in containments is an important challenge for analytical methods in the field of safety and security. Opening a package without knowledge of its contents and the resulting hazards is highly involved with risks and should be avoided whenever possible. Therefore, preferable methods work non-destructive with minimal interaction and are capable of identifying target substances in a containment quickly and reliably. Most spectroscopic methods find their limits, if the target substance is shielded by a covering material. To solve this problem, a combined laser drilling method with subsequent identification of the target substance by means of Raman spectroscopic measurements through microscopic bore holes of the covering material is presented. A pulsed laser beam is used for both the drilling process and as an excitation source for Raman measurements in the same optical setup. Results show the ability of this new method to gain high-quality spectra even when performed through microscopic small bore channels. With the laser parameters chosen right, the method can even be performed on highly sensitive explosives like triacetone triperoxide (TATP). Another advantageous effect arises in an observed reduction in unwanted fluorescence signal in the spectral data, resulting from the confocal-like measurement setup with the bore hole acting as aperture. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Modern production systems face enormous challenges due to rising customer requirements resulting in complex production systems. The operational efficiency in the competitive industry is ensured by an adequate production control system that manages all operations in order to optimize key performance indicators. Currently, control systems are mostly based on static and model-based heuristics, requiring significant human domain knowledge and, hence, do not match the dynamic environment of manufacturing companies. Data-driven reinforcement learning (RL) showed compelling results in applications such as board and computer games as well as first production applications. This paper addresses the design of RL to create an adaptive production control system by the real-world example of order dispatching in a complex job shop. As RL algorithms are "black box" approaches, they inherently prohibit a comprehensive understanding. Furthermore, the experience with advanced RL algorithms is still limited to single successful applications, which limits the transferability of results. In this paper, we examine the performance of the state, action, and reward function RL design. When analyzing the results, we identify robust RL designs. This makes RL an advantageous control system for highly dynamic and complex production systems, mainly when domain knowledge is limited. [ABSTRACT FROM AUTHOR]

The present work describes the results achieved during a study aiming at the full replacement of the natural gas demand of an integrated hot metal production. This work implements a novel approach using a biomass gasification plant combined with an electrolysis unit to substitute the present natural gas demand of an integrated hot metal production. Therefore, a simulation platform, including mathematical models for all relevant process units, enabling the calculation of all relevant mass and energy balances was created. As a result, the calculations show that a natural gas demand of about 385 MW can be replaced and an additional 100 MW hydrogen-rich reducing gas can be produced by the use of 132 MW of biomass together with 571 MW electricity produced from renewable energy. The results achieved indicate that a full replacement of the natural gas demand would be possible from a technological point of view. At the same time, the technological readiness level of available electrolysis units shows that a production at such a large scale has not been demonstrated yet. [ABSTRACT FROM AUTHOR]

Copyright of BHM Berg- und Hüttenmännische Monatshefte is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Infants < 51 weeks post-menstrual age (< 51 PMA) are often referred for modified barium swallow (MBS) studies for suspected silent aspiration (SA) given a possible association between SA and aspiration pneumonia. Infants this young are unlikely to have developed a mature laryngeal cough reflex, most likely rendering SA an expected finding in those who aspirate. The aims of this retrospective review were to (1) determine if SA resolves in a significant proportion of infants around the expected emergence of the laryngeal cough reflex, (2) determine which factors or characteristics are associated with and without SA resolution in these infants, and (3) determine if SA, or any aspiration, is associated with increased rates of lower respiratory infection (including aspiration pneumonia) in these infants. Results from the chart review revealed that 79/148 (53.4%) infants had SA on MBS < 51 PMA. 16/48 (33.3%) infants assessed for SA by the time of the expected emergence of the cough reflex had resolution. SA resolution was less common in infants with obstructive sleep apnea (p = 0.037). A total of 50/70 (71.4%) infants with a follow-up MBS had eventual SA resolution. Aspiration was not significantly associated with LRI, including aspiration pneumonia. The results suggested that the laryngeal cough reflex might develop later than reported in the literature and there is no association between aspiration and LRI. These findings may indicate that age should be considered before ordering an MBS solely to assess for SA in this population. The study provides preliminary evidence for future prospective research regarding SA resolution. [ABSTRACT FROM AUTHOR]

Purpose of Review: The orientation of the spine relative to the pelvis—particularly that in the sagittal plane—has been shown in both kinematic and radiographic studies to be paramount in governance of acetabular alignment during normal bodily motion. The purpose of this review is to better understand the challenges faced by arthroplasty surgeons in treating patients that have concurrent lumbar disease and are therefore more likely to have poorer clinical outcomes after THA than in patients without disease. Recent Findings: The concept of an "acetabular safe zone" has been well described in the past regarding the appropriate orientation of acetabular component in THA. However, this concept is now under scrutiny, and rising forth is a concept of functional acetabular orientation that is based on clinically evaluable factors that are patient and motion specific. Summary: The interplay between the functional position of the acetabulum and the lumbar spine is complex. The challenges that are thereby faced by arthroplasty surgeons in terms of proper acetabular cup positioning when treating patients with concomitant lumbar disease need to be better understood and studied, so as to prevent catastrophic and costly complications such as periprosthetic joint dislocations and revision surgeries. [ABSTRACT FROM AUTHOR]

Precision tissue diagnostics rely on high quality input specimens so that assay results are not affected by artifact, but advances in collection and processing of tissue specimens have lagged behind innovations in diagnostic assay development. Therefore, we have designed and evaluated a novel surgical tissue collection device that maintains and monitors sample temperature and motion throughout transport so that the major preanalytical variable of tissue temperature can be controlled and measured. This device, in combination with an improved cold-hot tissue fixation protocol affords optimal biomarker preservation in less overall time, thereby simultaneously improving diagnostic quality and turnaround time. We collected 50 primary and metastatic liver tumors using a novel transport device. Tissue was fixed using a rapid cold-hot fixation protocol and immunohistochemical assays were used to assess the performance of the device, in comparison to control tissue preserved using standard clinical fixation protocol. Two pathologists evaluated the IHC studies in a blinded fashion to determine the immunophenotype of each tumor. The observed IHC staining intensities and the clinical impressions of the immunophenotypes did not differ between tissue collected with the novel device and control tissue, while improvements in processing time were achieved. The novel cold transport device and rapid fixation protocol can be successfully and safely combined and used to monitor specimen conditions, thus preserving the diagnostic utility of specimens and improving the overall turn-around time of the diagnostic process. [ABSTRACT FROM AUTHOR]

Phosphoproteins are the key indicators of signaling network pathway activation. Many disease treatment therapies are designed to inhibit these pathways and effective diagnostics are required to evaluate the efficacy of these treatments. Phosphoprotein IHC have been impractical for diagnostics due to inconsistent results occurring from technical limitations. We have designed and tested a novel cold transport device and rapid cold plus warm formalin fixation protocol using phosphoproteins IHC. We collected 50 liver tumors that were split into two experimental conditions: 2 + 2 rapid fixation (2 hours cold then 2 hour warm formalin) or 4 hour room-temperature formalin. We analyzed primary hepatocellular carcinoma (n = 10) and metastatic gastrointestinal tumors (n = 28) for phosphoprotein IHC markers pAKT, pERK, pSRC, pSTAT3, and pSMAD2 and compared them to slides obtained from the clinical blocks. Expression of pERK and pSRC, present in the metastatic colorectal carcinoma, were better preserved with the rapid processing protocol while pSTAT3 expression was detected in hepatocellular carcinoma. Differences in pSMAD2 expression were difficult to detect due to the ubiquitous nature of protein expression. There were only 3 cases expressing pAKT and all exhibited a dramatic loss of signal for the standard clinical workflow. The rapid cold preservation shows improvement in phosphoprotein preservation. [ABSTRACT FROM AUTHOR]

We compared the acute effect of typical (haloperidol) and atypical (aripiprazole, clozapine, olanzapine) antipsychotic drugs (APDs) on spontaneous electrophysiological activity of in vitro neuronal networks cultured on microelectrode arrays (MEAs). Network burst analysis revealed a "regularizing" effect of all APDs at therapeutic concentrations, i.e., an increase of network-wide temporal synchronization. At supratherapeutic concentrations, all APDs but olanzapine mediated a decrease of burst and spike rates, burst duration, number of spikes in bursts, and network synchrony. The rank order of potency of APDs was: haloperidol > aripiprazole > clozapine > olanzapine (no suppression). Disruption of network function was not due to enhanced cell death as assessed by trypan blue staining. APDs promoted distinct concentration-dependent alterations yielding acute effect fingerprints of the tested compounds. These effects were rather characteristic for individual compounds than distinctive for typical vs. atypical APDs. Thus, this dichotomy may be of value in distinguishing clinical features but has no apparent basis on the network or local circuitry level. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis is a devastating motor neuron disease and to this day not curable. While 5-10% of patients inherit the disease (familiar ALS), up to 95% of patients are diagnosed with the sporadic form (sALS). ALS is characterized by the degeneration of upper motor neurons in the cerebral cortex and of lower motor neurons in the brainstem and spinal cord. The wobbler mouse resembles almost all phenotypical hallmarks of human sALS patients and is therefore an excellent motor neuron disease model. The motor neuron disease of the wobbler mouse develops over a time course of around 40 days and can be divided into three phases: p0, presymptomatic; p20, early clinical; and p40, stable clinical phase. Recent findings suggest an essential implication of the NAD+-producing enzyme Nmnat2 in neurodegeneration as well as maintenance of healthy axons. Here, we were able to show a significant downregulation of both gene and protein expression of Nmnat2 in the spinal cord of the wobbler mice at the stable clinical phase. The product of the enzyme NAD+ is also significantly reduced, and the values of the reactive oxygen species are significantly increased in the spinal cord of the wobbler mouse at p40. Thus, the deregulated expression of Nmnat2 appears to have a great influence on the cellular stress in the spinal cord of wobbler mice. [ABSTRACT FROM AUTHOR]

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Agricultural intensification is a major driver of biodiversity decline in many species including arthropods. This may also affect important ecosystem services such as natural pest regulation. Traditional grapevine varieties rely on a high number of fungicide applications, which can be greatly reduced in novel fungus resistant cultivars. Additionally, in contrast to the traditional trellis system, the semi-minimal pruned hedge offers a structurally more diverse habitat for arthropods. We investigated natural control of the grapevine pest Lobesia botrana ([Denis & Schiffermüller], 1775) (Lepidoptera: Tortricidae) with artificial inoculation of grape bunches, egg baits, camera surveillance and beatsheet sampling of predators. Reduced fungicide applications enhanced densities of L. botrana predators along with increased egg predation and reduced damage of inoculated grape bunches. Minimal pruning did not have a clear effect. Improved pest control potential adds to other advantages of reduced fungicide applications. Planting fungus-resistant varieties should be augmented, potentially also in other crop systems that rely heavily on fungicides. [ABSTRACT FROM AUTHOR]

Primary neurons are difficult to cultivate because they are often part of a complex tissue, and synaptically connected to numerous other cell types. These circumstances often prevent us from unveiling molecular and metabolic mechanisms of distinct cells, as functional signals or assays cannot clearly be correlated with them due to interfering signals from other parts of the culture. We therefore present an up-to-date method for obtaining a highly purified neuronal culture of Purkinje cells. In the past, Purkinje cells were successfully isolated from young mouse cerebella, but this protocol was never adapted to other mammals. We therefore provide an updated and adjusted protocol for Purkinje cell isolation from rat instead of mouse cerebella. To purify Purkinje cells, we obtained perinatal rat cerebella, dissociated them and performed a Percoll gradient centrifugation to segregate the smaller and larger cell fractions. In a second step, we performed an immunopanning procedure to enrich only Purkinje cells from the large cell fraction. Based on former protocols, we used a different antibody for the immunopanning procedure and adjusted several aspects from the initial protocol to improve the yield and vitality of Purkinje cells. We provide RT-qPCR-based purity data obtained with this protocol and show the behaviour and the growth of these purified Purkinje cells. We provide a highly reproducible purification protocol for Purkinje cell cultures of high purity that allows functional analysis and downstream assays on living rat Purkinje cells and further morphological growth analysis in future. [ABSTRACT FROM AUTHOR]

In a time where the training of new machine learning models is extremely time-consuming and resource-intensive and the sale of these models or the access to them is more popular than ever, it is important to think about ways to ensure the protection of these models against theft. In this paper, we present a method for estimating the similarity or distance between two black-box models. Our approach does not depend on the knowledge about specific training data and therefore may be used to identify copies of or stolen machine learning models. It can also be applied to detect instances of license violations regarding the use of datasets. We validate our proposed method empirically on the CIFAR-10 and MNIST datasets using convolutional neural networks, generative adversarial networks and support vector machines. We show that it can clearly distinguish between models trained on different datasets. Theoretical foundations of our work are also given. [ABSTRACT FROM AUTHOR]

Thymosin β4 (Tβ4), the principal G-actin regulating entity in eukaryotic cells, has also multiple intra- and extracellular functions related to tissue regeneration and healing. While its effect in adult organs is being widely investigated, currently, little is known about its influence on embryonic tissues, i.e., in the developing nervous system. The importance of Tβ4 for neural stem cell proliferation in the embryonic chicken optic tectum (OT) has previously been shown by us for the first time. In the present study, using in ovo electroporation, we carried out a quantification of the effects of the Tβ4-overexpression on the developing chicken OT between E4 and E6 at the hemisphere as well as cellular level. We precisely examined tissue growth and characterized cells arising from the elevated mitotic activity of progenitor cells. By using spinning-disk confocal laser scanning microscopy, we were able to visualize these effects across whole OT sections. Our experiments now demonstrate more clearly that the overexpression of Tβ4 leads to a tangential expansion of the treated OT-hemisphere and that, under these circumstances, overall density of tectal and in particular of postmitotic neuronal cells is increased. Thanks to this new quantitative approach, the present results extend our previous findings that Tβ4 is important for the proliferation of progenitor cells, neurogenesis, tangential expansion, and tissue growth in the young embryonic chicken optic tectum. Taken together, our results further illustrate and support the current idea that Tβ4 is widely implicated in shaping and maintenance of the nervous system. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are short noncoding RNAs of 19-25 nucleotides in length that regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs is associated with many disorders and neurodegenerative diseases affecting numerous different pathways and processes, of which many have not yet been completely explored. Recent studies even indicate a crucial role of miRNAs during brain development, with differential expression patterns of several miRNAs seen in both developing and mature cells. A miRNA profiling in brain tissue and the fundamental understanding of their effects might optimize the therapeutical treatment of various neurological disorders. In this study, we performed miRNA array analysis of enriched cerebellar Purkinje cell (PC) samples from both young and mature rat cerebella. We used laser microdissection (LMD) to enrich PC for a highly specific miRNA profiling. Altogether, we present the expression profile of at least 27 miRNAs expressed in rat cerebellar PC and disclose a different expression pattern of at least three of these miRNAs during development. These miRNAs are potential candidates for the regulation and control of cerebellar PC development, including neuritic and dendritic outgrowth as well as spine formation. [ABSTRACT FROM AUTHOR]

Various methods are available for DNA isolation from environmental samples. Because the chemical and biological composition of samples such as soil, sludge, or plant material is different, the effectiveness of DNA isolation can vary depending on the method applied and thus, have a substantial effect on the results of downstream analysis of the microbial community. Although the process of biogas formation is being intensely investigated, a systematic evaluation of kits for DNA isolation from material of biogas plants is still lacking. Since no DNA isolation kit specifically tailored for DNA isolation from sludge of biogas plants is available, this study compares five commercially available kits regarding their influence on downstream analyses such denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR (qPCR). The results show that not all kits are equally suited for the DNA isolation from samples of different biogas plants, but highly reproducible DGGE fingerprints as well as qPCR results across the tested samples from biogas reactors using different substrate compositions could be produced using selected kits. [ABSTRACT FROM AUTHOR]

Degradation of biomass in the absence of exogenous electron acceptors via anaerobic digestion involves a syntrophic association of a plethora of anaerobic microorganisms. The commercial application of this process is the large-scale production of biogas from renewable feedstock as an alternative to fossil fuels. After hydrolysis of polymers, monomers are fermented to short-chain fatty acids and alcohols, which are further oxidized to acetate. Carbon dioxide, molecular hydrogen (H), and acetate generated during the process are converted to methane by methanogenic archaea. Since many of the metabolic pathways as well as the syntrophic interactions and dependencies during anaerobic digestion involve formation, utilization, or transfer of H, its metabolism and the methanogenic population were assessed in various samples from three commercial biogas plants. Addition of H significantly increased the rate of methane formation, which suggested that hydrogenotrophic methanogenesis is not a rate-limiting step during biogas formation. Methanoculleus and Methanosarcina appeared to numerically dominate the archaeal population of the three digesters, but their proportion and the Bacteria-to- Archaea ratio did not correlate with the methane productivity. Instead, hydrogenase activity in cell-free extracts from digester sludge correlated with methane productivity in a positive fashion. Since most microorganisms involved in biogas formation contain this activity, it approximates the overall anaerobic metabolic activity and may, thus, be suitable for monitoring biogas reactor performance. [ABSTRACT FROM AUTHOR]