bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitizer: Automating Design and Evaluation of Neural Network Monitors
Authors: Azeem Muqsit , Grobelna Marta , Kanav Sudeep , Křetínský Jan , Mohr Stefanie , Rieder Sabine
Published: July 2024

The behavior of neural networks (NNs) on previously unseen types of data (out-of-distribution or OOD) is typically unpredictable. This can be dangerous if the network’s output is used for decision making in a safety-critical system. Hence, detecting that an input is OOD is crucial for the safe application of the NN. Verification approaches do not scale to practical NNs, making runtime monitoring more appealing for practical use. While various monitors have been suggested recently, their optimization for a given problem, as well as comparison with each other and reproduction of results, remain challenging.

We present a tool for users and developers of NN monitors. It allows for (i) application of various types of monitors from the literature to a given input NN, (ii) optimization of the monitor’s hyperparameters, and (iii) experimental evaluation and comparison to other approaches. Besides, it facilitates the development of new monitoring approaches. We demonstrate the tool’s usability on several use cases of different types of users as well as on a case study comparing different approaches from recent literature.
Guiding Enumerative Program Synthesis with Large Language Models
Authors: Li Yixuan , Parsert Julian , Polgreen Elizabeth
Published: July 2024

Pre-trained Large Language Models (LLMs) are beginning to dominate the discourse around automatic code generation with natural language specifications. In contrast, the best-performing synthesizers in the domain of formal synthesis with precise logical specifications are still based on enumerative algorithms. In this paper, we evaluate the abilities of LLMs to solve formal synthesis benchmarks by carefully crafting a library of prompts for the domain. When one-shot synthesis fails, we propose a novel enumerative synthesis algorithm, which integrates calls to an LLM into a weighted probabilistic search. This allows the synthesizer to provide the LLM with information about the progress of the enumerator, and the LLM to provide the enumerator with syntactic guidance in an iterative loop. We evaluate our techniques on benchmarks from the Syntax-Guided Synthesis (SyGuS) competition. We find that GPT-3.5 as a stand-alone tool for formal synthesis is easily outperformed by state-of-the-art formal synthesis algorithms, but our approach integrating the LLM into an enumerative synthesis algorithm shows significant performance gains over both the LLM and the enumerative synthesizer alone and the winning SyGuS competition tool.
History of toxicology at the Technical University of Munich (TUM)
Authors: Greim Helmut
Published: July 2024

Toxicology at the TUM is mainly associated with the Faculty of Medicine at the Klinikum rechts der Isar (MRI). The Department of Clinical Toxicology has been founded in 1963. Max von Clarmann, the head, focused his activities on the treatment of intoxications and the development of analytical methods and established a poison information center. His successors, Thomas Zielker and Florian Eyer, further developed this department to an internationally renown institution.

In 1967, the MRI became the TUM faculty of medicine with its Institute of Pharmacology and Toxicology. The director Melchior Reiter, formerly Institute of Pharmacology of the Ludwig Maximilians University (LMU), in 1970 initiated the foundation of the Department of Toxicology at the Gesellschaft für Strahlen- und Umweltforschung (GSF) with the director Gerhard Lange. The research focused on the neurotoxic effects of heavy metals and the metabolism and hepatoxicity of persistent chemicals. After Lange’s unexpected death in 1973, he was succeeded in 1975 by Helmut Greim from the University of Tübingen. The now Institute of Toxicology rapidly expanded developing and standardizing in vitro test methods, investigating the mechanism of carcinogens and mutagens and heavy metal toxicity. Training courses in the 15 major areas of toxicology have been organized at the GSF and competent centers in Germany. In 1987, Greim became the director of the newly founded Institute of Toxicology and Environmental Hygiene of the TUM, with expanded research and teaching activities, especially in toxicology at the faculties of Chemistry of the TUM and LMU, which thereafter became mandatory for students of chemistry at German universities.
Integration of secreted signaling molecule sensing on cell monitoring platforms: a critical review
Authors: Azuaje-Hualde Enrique , Alonso-Cabrera Juncal A. , de Pancorbo Marian M. , Benito-Lopez Fernando , Basabe-Desmonts Lourdes
Published: July 2024

Monitoring cell secretion in complex microenvironments is crucial for understanding cellular behavior and advancing physiological and pathological research. While traditional cell culture methods, including organoids and spheroids, provide valuable models, real-time monitoring of cell secretion of signaling molecules remains challenging. Integrating advanced monitoring technologies into these systems often disrupts the delicate balance of the microenvironment, making it difficult to achieve sensitivity and specificity. This review explored recent strategies for integrating the monitoring of cell secretion of signaling molecules, crucial for understanding and replicating cell microenvironments, within cell culture platforms, addressing challenges such as non-adherent cell models and the focus on single-cell methodologies. We highlight advancements in biosensors, microfluidics, and three-dimensional culture methods, and discuss their potential to enhance real-time, multiplexed cell monitoring. By examining the advantages, limitations, and future prospects of these technologies, we aim to contribute to the development of integrated systems that facilitate comprehensive cell monitoring, ultimately advancing biological research and pharmaceutical development.
Rapid detection of ricin at trace levels in complex matrices by asialofetuin-coated beads and bottom-up proteomics using high-resolution mass spectrometry
Authors: Piquet Paloma , Saadi Justyna , Fenaille François , Kalb Suzanne R. , Becher François
Published: July 2024

Ricin is a toxic protein regarded as a potential chemical weapon for bioterrorism or criminal use. In the event of a ricin incident, rapid analytical methods are essential for ricin confirmation in a diversity of matrices, from environmental to human or food samples. Mass spectrometry–based methods provide specific toxin identification but require prior enrichment by antibodies to reach trace-level detection in matrices. Here, we describe a novel assay using the glycoprotein asialofetuin as an alternative to antibodies for ricin enrichment, combined with the specific detection of signature peptides by high-resolution mass spectrometry. Additionally, optimizations made to the assay reduced the sample preparation time from 5 h to 80 min only. Method evaluation confirmed the detection of ricin at trace levels over a wide range of pH and in protein-rich samples, illustrating challenging matrices. This new method constitutes a relevant antibody-free solution for the fast and specific mass spectrometry detection of ricin in the situation of a suspected toxin incident, complementary to active ricin determination by adenine release assays.

Graphical Abstract
Analysis of shear creep properties of wood via modified Burger models and off-axis compression test method
Authors: Shimazaki Kanon , Ando Kosei
Published: July 2024

In this study, the rheological Burger model combining Maxwell and Voigt–Kelvin model units as well as modified mechanical models were employed to analyze the shear creep mechanism of wood. Off-axis compression tests were conducted on Japanese Hinoki cypress specimens (Chamaecyparis obtusa), and a mechanical analysis of the shear creep mechanism was performed. First, the measured creep compliance curves [JTL(t)] were fitted using this Burger model, which is a typical model used to explain the creep behavior of wood. Furthermore, three modified Burger models with non-Newtonian dashpots were proposed to explain the measured data more accurately: model 1—only the dashpot in the permanent strain unit is non-Newtonian; model 2—both dashpots are non-Newtonian; and model 3—only the dashpot in the delayed elastic strain unit is non-Newtonian. The mean value of the coefficient of determination was highest for model 1. The number of specimens that could be fitted with a tolerance error of 0.1% was 43 out of 50 with the Burger model, 45 with model 1, 25 with model 2, and 45 with model 3. The Burger model exhibited large discrepancies between the theoretical and measured values, model 2 could not be used to explain several specimens, and model 3 exhibited a delayed elastic strain behavior that was inconsistent with the definition. Therefore, we conclude that model 1 is the most appropriate for studying the shear creep behavior of wood.
Lattices of varieties of plactic-like monoids
Authors: Aird Thomas , Ribeiro Duarte
Published: July 2024

We study the equational theories and bases of meets and joins of several varieties of plactic-like monoids. Using those results, we construct sublattices of the lattice of varieties of monoids, generated by said varieties. We calculate the axiomatic ranks of their elements, obtain plactic-like congruences whose corresponding factor monoids generate varieties in the lattice, and determine which varieties are joins of the variety of commutative monoids and a finitely generated variety. We also show that the hyposylvester and metasylvester monoids generate the same variety as the sylvester monoid.
Carbon and Nutrient Limitations of Microbial Metabolism in Xingkai Lake, China: Abiotic and Biotic Drivers
Authors: Chen Xingting , Zhang Weizhen , Geng Mengdie , Shen Ji , Wang Jianjun
Published: July 2024

Microbial communities are crucial for water quality and biogeochemical cycling in freshwaters. Microbes secrete extracellular enzymes to decompose organic matter for their needs of nutrients and scarce elements. Yet, there is a lack of knowledge on microbial metabolic limitations in freshwaters, especially in lake sediments. Here, we examined the carbon, nitrogen, and phosphorus-acquiring extracellular enzyme activities and the bacterial and fungal communities of 30 sediments across Xingkai Lake, the largest freshwater lake in Northeast Asia. We further analyzed the microbial metabolic limitations via extracellular enzyme stoichiometry and explored the direct and indirect effects of abiotic and biotic factors on the limitations. We found that microbial metabolisms were primarily limited by phosphorus in Xingkai Lake. For instance, microbial carbon and phosphorus limitations were closely correlated to abiotic factors like water depth, total dissolved solids, sediment total carbon, and conductivity. The metabolic limitations were also affected by biotic factors, such as showing positive relationships with the alpha and beta diversity of bacteria, and with the beta diversity of fungi. In addition, community compositions of bacteria and fungi were mainly correlated to abiotic factors such as total carbon and dissolved organic carbon, respectively. Collectively, microbial metabolic limitations were affected directly or indirectly by abiotic factors and microbial communities. Our findings indicate that microbial metabolic limitations are not only driven by bacteria and fungi but also by abiotic factors such as water depth and total nitrogen, and thus provide empirical evidence for effective management of freshwater lakes under climate warming and intensified human activities.
Fungal aerosol and particulate matter in horse stables in Poland
Authors: Grzyb Jacek , Podstawski Zenon , Bulski Karol
Published: July 2024

Horses stay in different types of stables; especially during the cold season, they stay inside for most of the day. A stable is also a place where many people spend quite a lot of time either as employees who care for and train horses or as equine enthusiasts. Keeping horses in stables causes their constant exposure to high concentrations of particulate matter (PM) and molds in the air inside these facilities. The study was conducted in Udórz Stud Farm located in the southern region of Poland. It was carried out in two different types of stables: three runners and two box stables. The study continued for 2 years; samples were collected in each season of the year. The following devices were used: a six-stage Andersen-Graseby cascade impactor, the DustTrak™ II Aerosol Monitor 8530. The obtained results allowed for the conclusion that horses kept in box stables are exposed to lower concentrations of molds and yeasts than those kept in runners. Molds dominated in the stable air during humid periods—spring and autumn—while yeasts were more prominent during summer and winter. It was observed that cleaning stables reduces the morphotic elements of fungi in the air, even though it results in a higher level of particulate matter in the stable air. It should be noted that microclimate conditions were optimal for horses practically throughout the whole year.

Key points

• In stables, there is a high level of air intoxication, both by yeast and by mold fungi

• The concentrations of fungi in the air depend on the season and the stable cleaning procedure

• The PM concentrations depend on the type of stable
Exploring TNFi drug-levels and anti-drug antibodies during tapering among patients with inflammatory arthritis: secondary analyses from the randomised BIODOPT trial
Authors: Uhrenholt Line , Sørensen Mads E. R. , Lauridsen Karen B. , Duch Kirsten , Dreyer Lene , Christensen Robin , Hauge Ellen-Margrethe , Loft Anne Gitte , Rasch Mads N. B. , Horn Hans Christian , Taylor Peter C. , Nielsen Kaspar R. , Kristensen Salome
Published: July 2024

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: − 14% [95% CI − 27 to − 1%]) and more with low drug-levels (change: 18% [95% CI 5–31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA − 0.06 (95% CI − 0.44 to 0.33), PsA 0.03 (95% CI − 0.36 to 0.42), and axSpA 0.16 (− 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed.

Trial registration: EudraCT: 2017-001970-41, December 21, 2017.
RNA interference-based strategies to control Botrytis cinerea infection in cultivated strawberry
Authors: Capriotti Luca , Molesini Barbara , Pandolfini Tiziana , Jin Hailing , Baraldi Elena , Cecchin Michela , Mezzetti Bruno , Sabbadini Silvia
Published: July 2024

Key message

Gene silencing of BcDCL genes improves gray mold disease control in the cultivated strawberry.

Gene silencing technology offers new opportunities to develop new formulations or new pathogen-resistant plants for reducing impacts of agricultural systems. Recent studies offered the proof of concept that the symptoms of gray mold can be reduced by downregulating Dicer-like 1 (DCL1) and 2 (DCL2) genes of Botrytis cinerea. In this study, we demonstrate that both solutions based on dsRNA topical treatment and in planta expression targeting BcDCL1 and BcDCL2 genes can be used to control the strawberry gray mold, the most harmful disease for different fruit crops. 50, 70 and 100 ng μL−1 of naked BcDCL1/2 dsRNA, sprayed on plants of Fragaria x ananassa cultivar Romina in the greenhouse, displayed significant reduction of susceptibility, compared to the negative controls, but to a lesser extent than the chemical fungicide. Three independent lines of Romina cultivar were confirmed for their stable expression of the hairpin gene construct that targets the Bc-DCL1 and 2 sequences (hp-Bc-DCL1/2), and for the production of hp construct-derived siRNAs, by qRT-PCR and Northern blot analyses. In vitro and in vivo detached leaves, and fruits from the hp-Bc-DCL1/2 lines showed significantly enhanced tolerance to this fungal pathogen compared to the control. This decreased susceptibility was correlated to the reduced fungal biomass and the downregulation of the Bc-DCL1 and 2 genes in B. cinerea. These results confirm the potential of both RNAi-based products and plants for protecting the cultivated strawberry from B. cinerea infection, reducing the impact of chemical pesticides on the environment and the health of consumers.
The long-term learning curve of holmium laser enucleation of the prostate (HoLEP) in the en-bloc technique: a single surgeon series of 500 consecutive cases
Authors: Wenk M. J. , Hartung F. O. , Egen L. , Netsch C. , Kosiba M. , Grüne B. , Herrmann Jonas
Published: July 2024

Purpose

To evaluate perioperative parameters, clinical outcomes, and the learning curve of holmium laser enucleation of the prostate (HoLEP) of a single surgeon in 500 consecutive cases.

Methods

Demographic parameters, outcomes, and adverse events were evaluated. The learning curve for HoLEP in en-bloc technique of the first 500 consecutive patients was analyzed in clusters of 100 (clusters 1–5) using the Wilcoxen rank test, Chi² test and Kruskal Wallis test.

Results

Enucleation weight was similar in the clusters 1,2,3, and 5 (62 g, 63 g, 61 g, 61 g), in cluster 4 it was slightly higher at 73 g. There was a significant reduction in operating time from 67 min (cluster 1) to 57 min (cluster 2), 46 min (cluster 3), 53 min (cluster 4), and 43 min (cluster 5), p < 0.001. Enucleation efficiency (g/min) showed a steady increase (1.72, 2.24, 2.79, 2.92 vs. 2.99, p < 0.001). Laser energy efficiency also improved (2.17 vs. 2.12 vs. 1.71 vs. 1.65 vs. 1.55; p < 0.001). There was no measurable learning curve regarding the length of hospital stay (mean 2.5 days), catheterization time (1.9 days), hemoglobin drop (approx. 1 g/dl) or complications (p > 0.1).

Conclusions

HoLEP using the en-bloc technique is a safe and highly effective method. Over time, a slight but steady learning curve and improvement in operation time, enucleation efficiency and laser energy efficiency were shown even for an experienced surgeon - after 500 cases, still no plateau was reached. There was no measurable learning curve regarding blood loss, complications, length of hospital stay, and catheterization time.
The role of VI-RADS scoring criteria for predicting oncological outcomes in bladder cancer
Authors: Kozikowski Mieszko , Zagrodzka Magdalena , Zawadzki Marek , Zugaj Przemysław , Osiecki Rafał , Rzymkowski Franciszek , Śledź Mateusz , Sosnowski Roman , Dobruch Jakub , Giudice Francesco Del , Krajewski Wojciech
Published: July 2024

Purpose

Our purpose was to evaluate the prognostic value of Vesical Imaging Reporting and Data System (VI-RADS) in bladder cancer (BCa) staging and predicting recurrence or progression.

Methods

We retrospectively analyzed the prospectively collected data from 96 patients with bladder tumors who underwent VI-RADS-based multiparametric magnetic resonance imaging (mpMRI) before endourological treatment from April 2021 to December 2022. Diagnostic performance was evaluated by comparing mpMRI reports with final pathology, using logistic regression for muscle-invasive bladder cancer (MIBC) predictors. Follow-up until May 2023 included Kaplan-Meier and Cox regression analysis to assess VI-RADS predictive roles for recurrence-free survival (RFS) and progression-free survival (PFS).

Results

A total of 96 patients (19.8% women, 80.2% men; median age 68.0 years) were included, with 71% having primary tumors and 29% recurrent BCa. Multiparametric MRI exhibited high sensitivity (92%) and specificity (79%) in predicting MIBC, showing no significant differences between primary and recurrent cancers (AUC: 0.96 vs. 0.92, P = .565). VI-RADS emerged as a key predictor for MIBC in both univariate (OR: 40.3, P < .001) and multivariate (OR: 54.6, P < .001) analyses. Primary tumors with VI-RADS ≥ 3 demonstrated significantly shorter RFS (P = .02) and PFS (P = .04).

Conclusions

In conclusion, mpMRI with VI-RADS has a high diagnostic value in predicting MIBC in both primary and recurrent BCa. A VI-RADS threshold ≥ 3 is a strong predictor for MIBC, and in primary tumors predicts early recurrence and progression.
Visualization of the two-phase flow in the air gap of an optically accessible generic electric motor and its effect on torque
Authors: Auernhammer A. , Schary S. , Dreizler A. , Böhm B.
Published: July 2024

Electric motors with high-power densities are required for the implementation of electromobility. To achieve this, direct liquid cooling methods are increasingly being considered, in which oil is injected into the motor compartment. This results in a two-phase flow that can be used for efficient cooling. However, the oil, which can also penetrate the air gap between the rotor and stator, can also lead to additional losses due to increased friction. Since little is known about the two-phase flow in such systems, especially in the air gap, it is investigated by means of simple optical visualizations and high-speed laser-induced fluorescence imaging as well as torque measurements. The measurements are carried out in the air gap of an optically accessible generic model of a directly cooled electric motor. Speed variations were performed from 100 to 2000 rpm, and three different two-phase flow regimes were observed. At low speeds (Flow Regime 1), the air gap is filled locally with oil in radial direction, in the medium speed range (Flow Regime 2) with foam, while at high speeds (Flow Regime 3) separated films were observed on the rotor and stator. The torque difference between the two-phase and single-phase operation, which quantifies the mechanical losses due to the injected oil, increased continuously due to the oil in the air gap until it reached a maximum in Flow Regime 2 due to foam formation. In Flow Regime 3, the torque difference was negative. This was attributed to the fact that the grooves in the stator were filled with oil, thus reducing the turbulence generation of the air flow.
Role of blood metabolites in mediating the effect of gut microbiome on the mutated-RAS/BRAF metastatic colorectal cancer-specific survival
Authors: Xiang Yaoxian , Zhang Chan , Wang Jing , Cheng Yurong , Wang Kangjie , Wang Li , Tong Yingying , Yan Dong
Published: July 2024

Background

Recent studies have linked alterations in the gut microbiome and metabolic disruptions to the invasive behavior and metastasis of colorectal cancer (CRC), thus affecting patient prognosis. However, the specific relationship among gut microbiome, metabolite profiles, and mutated-RAS/BRAF metastatic colorectal cancer (M-mCRC) remains unclear. Furthermore, the potential mechanisms and prognostic implications of metabolic changes induced by gut microbiome alterations in patients with M-mCRC still need to be better understood.

Methods

We conducted Mendelian randomization (MR) to evaluate the causal relationship of genetically predicted 196 gut microbiome features and 1400 plasma metabolites/metabolite ratios on M-mCRC-specific survival. Additionally, we identified significant gut microbiome-metabolites/metabolite ratio associations based on M-mCRC. Metabolite information was annotated, and functional annotation and pathway enrichment analyses were performed on shared proteins corresponding to significant metabolite ratios, aiming to reveal potential mechanisms by which gut microbiome influences M-mCRC prognosis via modulation of human metabolism.

Results

We identified 11 gut microbiome features and 49 known metabolites/metabolite ratios correlated with M-mCRC-specific survival. Furthermore, we identified 17 gut microbiome-metabolite/metabolite ratio associations specific to M-mCRC, involving eight lipid metabolites and three bilirubin degradation products. The shared proteins corresponding to significant metabolite ratios were predominantly localized within the integral component of the membrane and exhibited enzymatic activities such as glucuronosyltransferase and UDP-glucuronosyltransferase, crucial in processes such as glucuronidation, bile secretion, and lipid metabolism. Moreover, these proteins were significantly enriched in pathways related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions, steroid hormone biosynthesis, and bile secretion.

Conclusion

Our study offers novel insights into the potential mechanisms underlying the impact of the gut microbiome on the prognosis of M-mCRC. These findings serve as a meaningful reference for exploring potential therapeutic targets and strategies in the future.
Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2
Authors: Chen Sha , Wang Qian , Bakker Diane , Hu Xin , Zhang Liping , van der Made Ingeborg , Tebbens Anna M. , Kovácsházi Csenger , Giricz Zoltán , Brenner Gábor B. , Ferdinandy Peter , Schaart Gert , Gemmink Anne , Hesselink Matthijs K. C. , Rivaud Mathilde R. , Pieper Michael P. , Hollmann Markus W. , Weber Nina C. , Balligand Jean-Luc , Creemers Esther E. , Coronel Ruben , Zuurbier Coert J.
Published: July 2024

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier that the protective mechanisms of the SGLT2i Empagliflozin (EMPA) are mediated through reductions in the sodium hydrogen exchanger 1 (NHE1)-nitric oxide (NO) pathway, independent of SGLT2. Here, we examined the role of SGLT2, NHE1 and NO in a murine TAC/DOCA model of HF. SGLT2 knockout mice only showed attenuated systolic dysfunction without having an effect on other signs of HF. EMPA protected against systolic and diastolic dysfunction, hypertrophy, fibrosis, increased Nppa/Nppb mRNA expression and lung/liver edema. In addition, EMPA prevented increases in oxidative stress, sodium calcium exchanger expression and calcium/calmodulin-dependent protein kinase II activation to an equal degree in WT and SGLT2 KO animals. In particular, while NHE1 activity was increased in isolated cardiomyocytes from untreated HF, EMPA treatment prevented this. Since SGLT2 is not required for the protective effects of EMPA, the pathway between NHE1 and NO was further explored in SGLT2 KO animals. In vivo treatment with the specific NHE1-inhibitor Cariporide mimicked the protection by EMPA, without additional protection by EMPA. On the other hand, in vivo inhibition of NOS with L-NAME deteriorated HF and prevented protection by EMPA. In conclusion, the data support that the beneficial effects of EMPA are mediated through the NHE1-NO pathway in TAC/DOCA-induced heart failure and not through SGLT2 inhibition.
Voice quality after open partial horizontal laryngectomy vs. total laryngectomy with voice prosthesis: a comparative study
Authors: Botti Cecilia , Lotto Cecilia , Tesauro Paolo , Guidotti Monica , Borghi Aurora , Molteni Gabriele , Presutti Livio , Fernandez Ignacio Javier
Published: July 2024

Objectives

The aim of this study is to compare voice outcomes in open partial horizontal laryngectomy vs. total laryngectomy (TL) with voice prosthesis.

Methods

In this retrospective monocentric study patients undergoing OPHL or TL with voice prosthesis were enrolled during the usual oncological follow-up consultations at the Otolaryngology and Audiology Unit of a University Hospital in the period between July 2022 and June 2023. Acoustic analysis (F0, HNR, NHR), maximum phonation time, I-SECEL and INFV0 scale were used to assess voice outcome.

Results

Forty-three patients were enrolled. Voices of patients undergoing LT were better in quality of voice (V0) at INFV0 scale. The scores in I-SECEL and acoustic analysis were comparable.

Conclusions

Voice quality could be slight better in patients undergoing TL with voice prosthesis than those undergoing OPHL.
Determining the cut-off value for the Minimal Documentation System (MIDOS2) screening tool to initiate specialized palliative care based on patient’s subjective need for palliative support and symptom burden in inpatients with advanced cancer
Authors: Heinzelmann Anna , Tewes Mitra , Müller Sandy , Sure Ulrich , Herrmann Ken , Schadendorf Dirk , Warnecke Eva , Rausch Raya , Skoda Eva-Maria , Salvador Comino Maria Rosa
Published: July 2024

Purpose

The Minimal Documentation System (MIDOS2) is recommended as a systematic screening tool for assessing symptom burden and patient needs in advanced cancer patients. Given the absence of an optimal weighting of individual symptoms and a corresponding cut-off value, this study aims to determine a threshold based on inpatient’s subjective need for palliative support. Additionally, we investigate the correlation between symptom burden and subjective need for palliative support collected through a patient-reported outcome measure (PROM) with survival duration of less or more than one year.

Methods

Inpatients diagnosed with advanced solid cancer completed an electronic PROM, which included the MIDOS2 questionnaire among other tools. Differences in symptom burden were analysed between patients expressing subjective need for palliative support and those with survival of less or more than one year using ANOVA, Mann–Whitney-U Test, logistic regression, Pearson and Spearman correlation tests. Cut-off analyses were performed using a ROC curve. Youden-Index, sensitivity, and specificity measures were used as well.

Results

Between April 2020 and March 2021, 265 inpatients were included in the study. Using a ROC curve, the MIDOS2 analysis resulted in an Area under the curve (AUC) of 0.732, a corresponding cut-off value of eight points, a sensitivity of 76.36% and a specificity of 62.98% in assessing the subjective need for palliative support. The MIDOS2, with double weighting of the significant symptoms, showed a cut-off value of 14 points, achieving a sensitivity of 78.18% and a specificity of 72.38%. A total of 55 patients (20.8%) expressed a need for support from the palliative care team. This need was independent of the oncological tumour entity and increased among patients with a survival of less than one year. These patients reported significantly poorer physical (p < 0.001) or mental (p < 0.001) condition. Additionally, they reported higher intensities of pain (p = 0.002), depressive symptoms (p < 0.001), weakness (p < 0.001), anxiety (p < 0.001), and tiredness (p < 0.001).

Conclusion

Using the established MIDOS2 cut-off value with an adjusted double weighting in our study, a large proportion of inpatients may be accurately referred to SPC based on their subjective need for palliative support. Additionally, subjective reports of poor general, mental, and physical condition, as well as pain, depressive symptoms, weakness, anxiety, and tiredness, increase the subjective need for palliative support, particularly in patients with a survival prognosis of less than one year.
Spiramycin-loaded maltodextrin nanoparticles as a promising treatment of toxoplasmosis on murine model
Authors: Abdel-Wahab Ayman A. , Shafey Dalia A. , Selim Sahar M. , Sharaf Soraya A. , Mohsen Khloud K. , Allam Dina M. , Elkhadry Sally W. , Gouda Marwa A.
Published: July 2024

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.

Graphical Abstract
Retrospective assessment of short-term outcomes of robotic- versus laparoscopic-assisted duodenal diamond anastomosis in neonates
Authors: Yang Si-Si , Lv Chengjie , Huang Shoujiang , Tou Jin-Fa , Lai Deng-Ming
Published: July 2024

Objective

The purpose of this study was to retrospectively compare the short-term outcomes of robotic- (RAD) and laparoscopic-assisted duodenal diamond-shaped anastomosis (LAD) in neonates.

Methods

Neonates who underwent RAD (n = 30) or LAD (n = 38) between January 2019 and December 2022 were analyzed retrospectively. Major patient data were collected, including preoperative, intraoperative, and postoperative information.

Results

All patients were neonates below the age of 30 days weighing 4 kg. Thirty (44.1%) neonates underwent RAD and 38 neonates (55.9%) underwent LAD. Compared to the LAD group, the RAD group had a shorter intra-abdominal operation time (RAD, 60.0(50.0 ~ 70.0) min; LAD, 79.9(69.0 ~ 95.3) min; p < 0.001). There were no significant differences in immediate and 30-day complications between the two groups.

Conclusions

RAD is safe and effective in neonates. Compared to traditional LAD, RAD showed comparable results.

Graphical abstract
Inference on process capability index $$S_{pmk}$$ for a new lifetime distribution
Authors: Karakaya Kadir
Published: July 2024

In various applied disciplines, the modeling of continuous data often requires the use of flexible continuous distributions. Meeting this demand calls for the introduction of new continuous distributions that possess desirable characteristics. This paper introduces a new continuous distribution. Several estimators for estimating the unknown parameters of the new distribution are discussed and their efficiency is assessed through Monte Carlo simulations. Furthermore, the process capability index $$S_{pmk}$$

S

pmk

is examined when the underlying distribution is the proposed distribution. The maximum likelihood estimation of the $$S_{pmk}$$

S

pmk

is also studied. The asymptotic confidence interval is also constructed for $$S_{pmk}$$

S

pmk

. The simulation results indicate that estimators for both the unknown parameters of the new distribution and the $$S_{pmk}$$

S

pmk

provide reasonable results. Some practical analyses are also performed on both the new distribution and the $$S_{pmk}$$

S

pmk

. The results of the conducted data analysis indicate that the new distribution yields effective outcomes in modeling lifetime data in the literature. Similarly, the data analyses performed for $$S_{pmk}$$

S

pmk

illustrate that the new distribution can be utilized for process capability indices by quality controllers.
$$\mu $$XL: explainable lead generation with microservices and hypothetical answers
Authors: Cruz-Filipe Luís , Kostopoulou Sofia , Montesi Fabrizio , Vistrup Jonas
Published: July 2024

Lead generation refers to the identification of potential topics (the ‘leads’) of importance for journalists to report on. In this article we present $$\mu $$
μ
XL, a new lead generation tool based on a microservice architecture that includes a component of explainable AI. $$\mu $$
μ
XL collects and stores historical and real-time data from web sources, like Google Trends, and generates current and future leads. Leads are produced by a novel engine for hypothetical reasoning based on temporal logical rules, which can identify propositions that may hold depending on the outcomes of future events. This engine also supports additional features that are relevant for lead generation, such as user-defined predicates (allowing useful custom atomic propositions to be defined as Java functions) and negation (needed to specify and reason about leads characterized by the absence of specific properties). Our microservice architecture is designed using state-of-the-art methods and tools for API design and implementation, namely API patterns and the Jolie programming language. Thus, our development provides an additional validation of their usefulness in a new application domain (journalism). We also carry out an empirical evaluation of our tool.
Identifying the influence of climate policy uncertainty and oil prices on modern renewable energies: novel evidence from the United States
Authors: Karlilar Pata Selin , Balcilar Mehmet
Published: July 2024

The policy uncertainty surrounding climate change can intensify the urgency of implementing climate policies and influence investment decisions, thereby serving as a catalyst for policy transformation. In this context, given its withdrawal from and subsequent re-commitment to the Paris Agreement, the United States (US) may experience policy uncertainty over climate change. Given this backdrop, it is of paramount importance to explore how the uncertainties caused by shifts in climate policy affect clean energy. This study delves into the impact of climate policy uncertainty and oil prices on modern renewable energy sources, such as solar, wind, geothermal, and biofuels. The most recent monthly data from 1989 to 2023 are used by conducting the Residual Augmented Least Squares (RALS) methodology. The empirical findings show that the uncertainty surrounding climate policy is leading to a shift in the US energy composition, with a focus on solar energy, wind energy, and biofuels. Moreover, the fluctuation in oil prices has a significant effect on the deployment of wind and biofuels, but no discernible effect on solar power. These findings provide significant insights for aligning climate policy in the US with Sustainable Development Goal (SDG) 7, highlighting the crucial importance of encouraging investments in solar energy, wind energy, and biofuels.

Graphical abstract
Could Photobiomodulation help lactating women and their newborns?
Authors: Elseody Maha Helmy Ammar Ahmed , Mohamed Marwa Abd El-Rahman , Alsharnoubi Jehan
Published: July 2024

During the first several weeks following lactation, nipple pain frequently prevents mothers from continuing breastfeeding. To evaluate the efficacy of using Photobiomodulation (PBM) versus anti-inflammatory topical cream, on inflamed nipple, and the effect on milk production. This study was carried-out on 50 breastfeeding women with nipple pain and fissure. Our patients were divided into two groups ; study group (Group I): 25 patients received 12 sessions of PBM using Diode laser for a period of 4 weeks, 3 sessions per week every alternative day, and controlled group (Group II): 25 patients used Anti-inflammatory topical cream. Regarding inflammatory signs in both groups, Group I showed a significant decrease in redness compared to Group II at the 3rd and 4th week, and a significant decrease in nipple fissure and pain at the 3rd week. There was a significant increase in milk amount reflected on the infant’s weight. We concluded that PBM was more effective in decreasing nipple pain, inflammation and subsequently milk production and infant weight than topical anti-inflammatory creams.
Broadening the horizon in land use change modelling: Normative scenarios for nature positive futures in Switzerland
Authors: Black Benjamin , Adde Antoine , Farinotti Daniel , Guisan Antoine , Külling Nathan , Kurmann Manuel , Martin Caroline , Mayer Paula , Rabe Sven-Erik , Streit Jan , Zekollari Harry , Grêt-Regamey Adrienne
Published: July 2024

Within scenario-based research of social-ecological systems, there has been a growing recognition of the importance of normative scenarios that define positive outcomes for both nature and society. While several frameworks exist to guide the co-creation of normative scenario narratives, examples of operationalizing these narratives in quantitative simulation modelling are still limited. To address this gap, this paper presents an example of how aspects of normative scenarios can be realized within a spatial model of land use and land cover change. This is achieved through a combination of data-driven approaches to encapsulate scenario-specific differences in local and global scale phenomena, as well as iterative expert elicitation to quantify descriptive trends from narratives. This approach is demonstrated with a case study simulating five scenarios of landscape change (three normative and two exploratory) in Switzerland between 2020 and 2060. The resulting maps of future land use and land cover exhibited distinct variations between the scenarios, notably with regard to the prevalence of areas of heterogeneous semi-natural land, such as alpine pastures and grassland, often considered culturally emblematic of Switzerland. While the simulation results were generally consistent with the outcomes expressed in the scenario narratives, following a process of expert feedback, we reflect that there are clear challenges in leveraging such results to elicit further discussions as to the desirability and plausibility of future scenarios. Specifically, the need to summarize spatial simulations in a manner that is easily interpretable and encourages consideration of the broader patterns of change rather than focusing on fine-scale details.
Computed tomography based evaluation of the association between sphenoid sinus pneumatization patterns and variations of adjacent bony structures in relation to age and gender
Authors: Açar Gülay , Gökşan Ahmet Safa , Aydoğdu Demet
Published: July 2024

Many studies revealed that the sphenoid sinus pneumatization (SSP) affects the protrusion/dehiscence of adjacent structures including optic canal (OC), foramen rotundum (FR), vidian canal (VC), and carotid canal (CC). Knowledge of this relationship bears vital importance to identify the safest surgical route during transsphenoidal procedures. Therefore, we aimed to determine the individualized prevalence of the protrusion/dehiscence of adjacent structures based on sagittal and coronal SSP (SSSP and CSSP) patterns. Computed tomography images of 300 patients were analysed to identify the SSSP and CSSP types, and the protrusion/dehiscence of adjacent structures was determined. The relationship between the variables was examined using statistical analysis in terms of age, gender, and laterality. The most prevalent SSSP type was postsellar (62.7%), followed by sellar (30%), presellar (6.6%), and conchal (0.7%). In 71.3% of patients, five types of CSSP were observed, with 23.6% and 21.7% exhibiting Type IV and V, respectively. Our results indicated that postsellar type, Type IV and V CSSP associated with the highest likelihood of protrusion/dehiscence of OC, FR, VC, and CC. Furthermore, no significant correlation was observed between these qualitative variables and gender, with the exception of the VC dehiscence, the protrusion of OC and CC. No notable differences were identified with respect to laterality. Also, the probability of having postsellar type, Type IV and V CSSP, as well as the protrusion of OC, VC, and CC, decreased with increasing age. Further detailed analysis of this association is required to predict the size of the surgical window and to prevent neurovascular injury.
Novel Chromium–Silicon Slurry Coatings for Hot Corrosion Environments
Authors: Kerbstadt M. , Ma K. , White E. M. H. , Knowles A. J. , Galetz M. C.
Published: July 2024

Ni-based superalloys are commonly used in gas turbines because of their exceptional high-temperature mechanical properties. To secure a long service life, the materials must also have sufficient corrosion resistance. Therefore, diffusion coatings are widely used to enrich the surface in protective oxide scale-forming elements. For temperatures between 650 and 950 °C, where hot corrosion occurs, Cr-based coatings are advantageous. These are commonly applied via the laborious pack cementation process. Recently, a novel cost-effective Cr/Si slurry coating process has been developed which demonstrated resistance to oxidative high-temperature environments. Here, the protection of the slurry coatings against hot corrosion type I at 900 °C on the Ni-based superalloy Rene 80 is investigated and compared to coatings produced by pack cementation. Prior to the 300-h exposures in air containing 0.1% SO2 at 900 °C, 4 mg/cm2 of Na2SO4 was deposited on the material surfaces. The uncoated Rene 80 exhibited rapid dissolution of the initial oxide scale followed by catastrophic break away oxidation. In comparison, the slurry coatings showed significantly improved hot corrosion resistance compared to the uncoated alloy and a better protection than a Cr pack cementation coating. The Cr pack cemented Rene 80 showed improved hot corrosion resistance, but Cr depletion in the subsurface zone occurred with increasing exposure time, associated with the propagation of Al internal oxidation and increasing sulfidation. In contrast, the slurry coatings formed an external Cr2O3 scale coupled with an agglomeration of SiO2 underneath and a continuous Al2O3 subscale which offered a better diffusion barrier and leading to superior long-term protection against hot corrosion.
Advances in antitumour therapy with oncolytic herpes simplex virus combinations
Authors: Qi Xuejiao
Published: July 2024

Oncolytic Virus (OVs) is an emerging approach to tumour immunity that allows the use of natural or genetically modified viruses to specifically infect and lyse tumour cells without damaging normal cells. Oncolytic herpes simplex virus (oHSV) is one of the more widely researched and applied OVs in the field of oncology, which can directly kill tumour cells to promote anti-tumour immune responses. oHSV is one of the few viruses with good antiviral drugs, so oHSV is also more clinically safe. In recent years, in addition to monotherapy of oHSV in tumours, more and more studies have been devoted to exploring the anti-tumour effects of oHSV in combination with other therapeutic approaches. In this article we describe the progress of oHSV combination therapy against tumours in the nervous system, digestive system, reproductive system and other systems.