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The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities. Various stages of computational and chemical biology research can benefit from this knowledge. The search for putative off-targets and the establishment of polypharmacological effects by comparing binding sites led to promising results for numerous projects. Although many cavity comparison methods are available, a comprehensive analysis to guide the choice of a tool for a specific application is wanting. Moreover, the broad variety of binding site modeling approaches, comparison algorithms, and scoring metrics impedes this choice. Herein, we aim to elucidate strengths and weaknesses of binding site comparison methodologies. A detailed benchmark study is the only possibility to rationalize the selection of appropriate tools for different scenarios. Specific evaluation data sets were developed to shed light on multiple aspects of binding site comparison. An assembly of all applied benchmark sets (ProSPECCTs-Protein Site Pairs for the Evaluation of Cavity Comparison Tools) is made available for the evaluation and optimization of further and still emerging methods. The results indicate the importance of such analyses to facilitate the choice of a methodology that complies with the requirements of a specific scientific challenge.

The article focuses on the findings of endurance tests on thrust bearings. In addition to the mechanical load (axial load: 10 ≤ C0/P ≤ 19, lubrication gap: 0.33 µm ≤ h0 ≤ 1.23 µm), these bearings are also exposed to electrical loads (voltage: 20 Vpp ≤ U0 ≤ 60 Vpp, frequency 5 kHz and 20 kHz), such as those generated by modern frequency converters. In a previous study, the focus was on the chemical change in the lubricant and the resulting wear particles. In contrast, this article focuses on the changes occurring in the metallic contact partners. Therefore, the changes in the surface topography are analysed using Abbott–Firestone curves. These findings show that tests with an additional electrical load lead to a significant reduction in roughness peaks. A correlation to acceleration measurements is performed. Moreover, it is shown that the electrical load possibly has an effect on the light load hardness. An increase in the occurring wear could not be detected during the test series. Also, a comparison with mechanical reference tests is made. The article finally provides an overview of different measurement values and their sensitivity to additional electrical loads in roller bearings.

Background Increasing life expectancy requires specific attention on geriatric patients. Data support a potential reduction of surgical morbidity for patients undergoing laparoscopic surgery as compared to conventional surgery. The aim of this study was to investigate the comparative effect of laparoscopic and open colorectal surgery on geriatric patients. Methods A systematic review of electronic information sources was undertaken. Studies that provided outcome data on patients aged 65 years or older, subjected to laparoscopic or open colorectal surgery, were considered. Mortality, morbidity, cardiac and pulmonary complications were the outcome measures of treatment effect. The methodological quality of selected studies was independently appraised by two reviewers. Random effects model was applied to synthesize outcome data. Results Twenty-seven articles providing data for 66,592 patients were included in the analysis. Patients undergoing laparoscopic surgery had a decreased risk for mortality (2.2 vs. 5.4 %; OR 0.55, 95 % CI 0.44–0.67), overall morbidity (19.3 vs. 26.7 %; OR 0.54, 95 % CI 0.46–0.63), cardiac (4.7 vs. 7.7 %; OR 0.60, 95 % CI 0.39–0.92) and respiratory complications (3.9 vs. 6.3 %; OR 0.67, 95 % CI 0.47–0.95). Sensitivity analysis including reports with similar age, American Society of Anesthesiologists score and/or similar prevalence of cardiopulmonary morbidity between the laparoscopic and the open treatment arm validated the outcome estimates of the primary analysis. Conclusions This analysis supports a substantial benefit for elderly patients undergoing laparoscopic in comparison with open colorectal surgery. The comparative effect of either approach on geriatric patients with pulmonary and cardiac comorbidities is a subject of further investigation.

Within this paper, electro-mechanical long-term tests on a thrust bearing were presented. The effects of an additional electrical load on the bearing raceways and the used lubricant were investigated. Chemical investigations and viscosity measurements were presented, which show the changes in the lubricant. These investigations were compared with the electrical loads and the occurring raceway damage. In addition, a comparison was made with mechanical reference tests. This procedure makes it possible to classify the changes that occur due to the electrical load and to distinguish the effects from each other. The background to these investigations is the increased occurrence of parasitic currents in electric motors, which can lead to damage to machine elements. The phenomena that occur here are new challenges in the development of drive trains.

In the presented work, a parametric multibody simulation model is presented that is capable of predicting the friction torque and kinematics of tapered roller bearings. For a highly accurate prediction of bearing friction, consideration of solid and lubricant friction is mandatory. For tapered roller bearings in particular, the friction in the contact between the rolling element and raceway is of importance. Friction forces in the contact between the rolling element end face and inner ring rib as well as roller cage pocket contacts are also considered in the model. A large number of tests were carried out to validate the model in terms of the simulated frictional torque. Influencing variables such as speed, axial load, radial load, and temperature were investigated. The simulation results show good agreement with the measured friction torque, which confirms that the model is well suited to predict frictional torques and therefore the kinematics of tapered roller bearings.

BackgroundPrevious studies suggest clinical effectiveness of endoscopic full-thickness plication in selected patients with gastroesophageal reflux disease (GERD). The aim of this study was to assess the clinical safety and efficiency of the GERDx™ device by evaluating clinical parameters, reflux symptom scores, and quality of life (QoL).MethodsProspective one-arm trial evaluating the outcome of forty patients with GERD subjected to endoscopic plication with the GERDx™ device. We included patients with at least one typical reflux symptom despite treatment with a PPI for > 6 months, pathologic esophageal acid exposure, hiatal hernia of size < 2 cm, and endoscopic Hill grade II–III. Evaluation of Gastrointestinal Quality of Life Index (GIQLI), symptom scores, esophageal manometry, and impedance-pH-monitoring were performed at baseline and at 3 months after surgery. (Trial Registration: ClinicalTrials.gov NCT 01798212.)ResultsThere were no intraoperative complications. Four out of forty patients experienced postoperative complications requiring intervention. Seven of forty patients were subjected to laparoscopic fundoplication 3 months after endoscopic plication due to persistent symptoms and were lost to further follow-up. Thirty out of forty patients were available at 3-month follow-up. There was an improvement of the GIQLI score, from a mean of 92.45 ± 18.47 to 112.03 ± 13.11 (p < 0.001). The general reflux-specific score increased from a mean of 49.84 ± 24.83 to 23.93 ± 15.63 (p < 0.001), and the DeMeester score from a mean of 46.48 ± 30.83 to 20.03 ± 23.62 (p < 0.001). There was no significant change in manometric data after intervention. Three of thirty patients continued daily antireflux medication.ConclusionsEndoscopic plication with the GERDx™ device reduced distal acid exposure of the esophagus, reflux-related symptoms, and improved GIQLI scores with minimal side effects in a selected cohort of patients and may be a safe alternative in the treatment of GERD.

Single-incision laparoscopic appendectomy has emerged as a less invasive alternative to conventional laparoscopic surgery. High-quality relevant evidence is limited. A systematic review of electronic information sources was undertaken, with the objective of identifying randomized trials that compared single-incision with conventional laparoscopic appendectomy. Outcome measures included 30-day morbidity, abdominal abscess, wound infection, open conversion, reoperation, operative time, length of hospital stay, and postoperative pain. Fixed-effects and random-effects models were used to calculate combined overall effect sizes of pooled data. Data are presented as odds ratios or weighted mean differences with 95% confidence intervals (CIs). Five randomized trials were identified, with a total of 746 patients. Thirty-day morbidity (9.6% vs 8.6%; odds ratio, 1.14; 95% CI, .69 to 1.89) and wound infection rates were similar between single-incision and conventional laparoscopy (4.0% vs 4.8%; odds ratio, .83; 95% CI, .41 to 1.68), whereas the duration of surgery was longer in the single-incision group (46.3 vs 40.7 minutes; weighted mean difference, 6.01; 95% CI, 2.26 to 9.76). Available data were not adequately robust to reach conclusions regarding the remaining outcome measures. Similar postoperative morbidity and wound infection rates for single-incision and conventional laparoscopic appendectomy are supported by the current literature, but single-incision surgery requires longer operative time.

Siamese networks, representing a novel class of neural networks, consist of two identical subnetworks sharing weights but receiving different inputs. Here we present a similarity-based pairing method for generating compound pairs to train Siamese neural networks for regression tasks. In comparison with the conventional exhaustive pairing, it reduces the algorithm complexity from O(n 2 ) to O(n). It also results in a better prediction performance consistently on the three physicochemical datasets, using a multilayer perceptron with the circular fingerprint as a proof of concept. We further include into a Siamese neural network the transformer-based Chemformer, which extracts task-specific features from the simplified molecular-input line-entry system representation of compounds. Additionally, we propose a means to measure the prediction uncertainty by utilizing the variance in predictions from a set of reference compounds. Our results demonstrate that the high prediction accuracy correlates with the high confidence. Finally, we investigate implications of the similarity property principle in machine learning. Graphical Abstract

Machine learning models using protein-ligand interaction fingerprints show promise as target-specific scoring functions in drug discovery, but their performance critically depends on the underlying decoy selection strategies. Recognizing this critical role in model performance, various decoy selection strategies were analyzed to enhance machine learning models based on the Protein per Atom Score Contributions Derived Interaction Fingerprint (PADIF). We explored three distinct workflows for decoy selection: (1) random selection from extensive databases like ZINC15, (2) leveraging recurrent non-binders from high-throughput screening (HTS) assays stored as dark chemical matter, and (3) data augmentation by utilizing diverse conformations from docking results. Active molecules from ChEMBL, combined with these decoy approaches, were used to train and test different machine learning models based on PADIF. The final validation was done by confirming experimentally determined inactive compounds from the LIT-PCBA dataset. Our findings reveal that models trained with random selections from ZINC15 and compounds from dark chemical matter closely mimic the performance of those trained with actual non-binders, presenting viable alternatives for creating accurate models in the absence of specific inactivity data. Furthermore, all models showed an enhanced ability to explore new chemical spaces for their specific target and enhanced the top active compound selection over classical scoring functions, thereby boosting the screening power in molecular docking. These findings demonstrate that appropriate decoy selection strategies can maintain model accuracy while expanding applicability to targets even when lacking extensive experimental data. Scientific contribution This study enhances the available options for decoys to create new bioactive machine learning classification models from public datasets. Through a molecular docking protocol and PADIF representation, we identify the benefits of using this methodology to improve binder selection in molecular docking