bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Forest Structures for Passive Automata Learning
Authors: Krumnow Arne , Plambeck Swantje , Fey Goerschwin
Published: June 2024

We present an extension on a passive learning algorithm for deterministic finite automata (DFAs) and Mealy machines which is based on the regular positive and negative inference (RPNI) algorithm. The extension builds a structure which is inspired by random forests. Instead of building a single automaton, the forest builds several. The paper introduces two forest structures for learning DFAs, together with their respective extension for Mealy machines, where the choice of which to pick depends on the output to achieve, as well as the type of application. Following that, the empirical analysis shows which parameters yield better results than the basic RPNI passive learning approach. In our experiments, forest structures for passive learning of automata yield significant improvement over the standard RPNI algorithm of up to $$43\%$$

43
%

in the total number of correct outputs when testing Mealy machines.
Unveiling chiral states in the XXZ chain: finite-size scaling probing symmetry-enriched c = 1 conformal field theories
Authors: Wei Chenan , Mkhitaryan Vagharsh V. , Sedrakyan Tigran A.
Published: June 2024

Abstract

We study the low-energy properties of the one-dimensional spin-1/2 XXZ chain with time-reversal symmetry-breaking pseudo-scalar chiral interaction and propose a phase diagram for the model. In the integrable case of the isotropic Heisenberg model with the chiral interaction, we employ the thermodynamic Bethe ansatz to find “chiralization”, the response of the ground state versus the strength of the pseudo-scalar chiral interaction of a chiral Heisenberg chain. Unlike the magnetization case, the chirality of the ground state remains zero until the transition point corresponding to critical coupling αc = 2J/π with J being the antiferromagnetic spin-exchange interaction. The central-charge c = 1 conformal field theories (CFTs) describe the two phases with zero and finite chirality. We show for this particular case and conjecture more generally for similar phase transitions that the difference between two emergent CFTs with identical central charges lies in the symmetry of their ground state (lightest weight) primary fields, i.e., the two phases are symmetry-enriched CFTs. At finite but small temperatures, the non-chiral Heisenberg phase acquires a finite chirality that scales with the temperature quadratically. We show that the finite-size effect around the transition point probes the transition.
Comprehensive analysis of 19 cannabinoids in commercial CBD oils: concentrations, profiles, and safety implications
Authors: Lindekamp Niklas , Weigel Stefan , Sachse Benjamin , Schäfer Bernd , Rohn Sascha , Triesch Nadja
Published: June 2024

Nineteen cannabinoids, including Δ9-THC (tetrahydrocannabinol) and CBD (cannabidiol), were quantified in 22 CBD oils, 2 CBG (cannabigerol) oils, and 2 CBN (cannabinol) oils, marketed as food supplements, aroma oils, or cosmetic preparations. Analyses were conducted using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The declared concentrations of CBD (or CBG, CBN) in the oils ranged from 2.5 to 20%. Actual concentrations compared to declared concentrations ranged from 81 to 226%. CBD concentrations of up to 9 mg per drop were found. Δ9-THC was detected in 20 of 26 samples, with concentrations ranging from 5 to 1576 mg/kg (mean = 536 mg/kg). Considering the highest daily intake suggested by one manufacturer (20 drops) and a body weight of 70 kg, the measured Δ9-THC concentration in 50% (n = 13) of the products would exceed the acute reference dose (ARfD) of 1 µg/kg body weight (bw) derived for Δ9-THC by the European Food Safety Authority (EFSA). For 7 samples, only 2 drops of oil would be sufficient to exceed the ARfD of Δ9-THC.
Novel role of NCoR1 in impairing spatial memory through the mediation of a novel interacting protein DEC2
Authors: Cheng Kuang-Min , Hsu Wei-Lun , Ma Yun-Li , Liu Yen-Chen , Lee Eminy H. Y.
Published: June 2024

Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation.
The effect of NAFTA on Mexico's wage gap
Authors: Arends-Kuenning Mary P. , Baylis Kathy , Garduño-Rivera Rafael
Published: June 2024

This paper studies how the North American Free Trade Agreement (NAFTA) affected the wage gap between high and low-paid workers within Mexico, considering internal migration. In low-skilled, labor-abundant developing countries, trade liberalization should theoretically increase the wages of low-skilled workers, decreasing income inequality. However, anecdotal evidence indicates that NAFTA increased the gap between rich and poor in Mexico, and empirical evidence is mixed (Hirte et al. 2020; Brülhart 2011; Bosch and Manacorda 2010; Nicita 2009; Chiquiar 2008; Hanson 2007; Gonzalez-Rivas 2007). Because trade may affect wages differently across regions within the country, accurate measures of wage effects must incorporate internal migration; otherwise, apparent wage convergence or divergence might only reflect a geographic resorting of workers. We evaluate wage changes by considering rural-to-urban migration. We first find a slight decrease in both internal and external migration in the years after NAFTA. Then, we find that all male workers see a wage reduction from trade openness, although the harm of high-wage workers almost doubled that of their counterparts with low wages. NAFTA also mitigated some of the wage differentials between the North and South. In summary, trade liberalization has reduced wage differentials among working-age men in urban areas.
Review of early ground deformation observations by electronic distance measurements (EDM) on active Sicilian volcanoes: valuable data and information for long-term analyses
Authors: Bonforte Alessandro , Gambino Salvatore , Velardita Rosanna , Privitera Laura
Published: June 2024

Electronic distance measurements (EDM) represent one of the first methods to detect ground deformation on volcanoes. Used since 1964, they enable acquiring precise distance measurements, whose time repetition may highlight changes related to volcanic activity. This technique was widely used on volcanoes from the 1970s to the early 2000s and has been used many times to model position, geometry, and volumes of magmatic and hydrothermal sources. This paper reports the EDM experiences, results and data acquired on Sicilian volcanoes (Etna, Vulcano, Stromboli and Pantelleria) from the early 1970s, which have played a major role in the birth of the volcano-geodesy for volcanic process knowledge, making the Sicilian volcanoes among those with the longest geodetic record in the world.
Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers
Authors: Hix-Janssens Thomas , Davies Julia R. , Turner Nicholas W. , Sellergren Börje , Sullivan Mark V.
Published: June 2024

Periodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer’s diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).
A novel biomimetic nanoplasmonic sensor for rapid and accurate evaluation of checkpoint inhibitor immunotherapy
Authors: Batool Razia , Soler Maria , Singh Rukmani , Lechuga Laura M.
Published: June 2024

Immune checkpoint inhibitors (ICIs) emerged as promising immunotherapies for cancer treatment, harnessing the patient’s immune system to fight and eliminate tumor cells. However, despite their potential and proven efficacies, checkpoint inhibitors still face important challenges such as the tumor heterogeneity and resistance mechanisms, and the complex in vitro testing, which limits their widespread applicability and implementation to treat cancer. To address these challenges, we propose a novel analytical technique utilizing biomimetic label-free nanoplasmonic biosensors for rapid and reliable screening and evaluation of checkpoint inhibitors. We have designed and fabricated a low-density nanostructured plasmonic sensor based on gold nanodisks that enables the direct formation of a functional supported lipid bilayer, which acts as an artificial cell membrane for tumor ligand immobilization. With this biomimetic scaffold, our biosensing approach provides real-time, highly sensitive analysis of immune checkpoint pathways and direct assessment of the blocking effects of monoclonal antibodies in less than 20 min/test. We demonstrate the accuracy of our biomimetic sensor for the study of the programmed cell death protein 1 (PD1) checkpoint pathway, achieving a limit of detection of 6.7 ng/mL for direct PD1/PD-L1 interaction monitoring. Besides, we have performed dose–response inhibition curves for an anti-PD1 monoclonal antibody, obtaining a half maximal inhibitory concentration (IC50) of 0.43 nM, within the same range than those obtained with conventional techniques. Our biomimetic sensor platform combines the potential of plasmonic technologies for rapid label-free analysis with the reliability of cell-based assay in terms of ligand mobility. The biosensor is integrated in a compact user-friendly device for the straightforward implementation in biomedical and pharmaceutical laboratories.

Graphical Abstract
Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0
Authors: Albert Nathalie L. , Preusser Matthias , Traub-Weidinger Tatjana , Tolboom Nelleke , Law Ian , Palmer Joshua D. , Guedj Eric , Furtner Julia , Fraioli Francesco , Huang Raymond Y. , Johnson Derek R. , Deroose Christophe M. , Herrmann Ken , Vogelbaum Michael , Chang Susan , Tonn Joerg-Christian , Weller Michael , Wen Patrick Y. , van den Bent Martin J. , Verger Antoine , Ivanidze Jana , Galldiks Norbert
Published: June 2024

Purpose

To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands.

Methods

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO).

Results

Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma.

Conclusion

These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576–87). The information provided should be considered in the context of local conditions and regulations.
TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma
Authors: Xue Han-Yue , Wei Fang
Published: June 2024

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to the TME in the pathogenesis of MM. Many researchers have identified that myeloma cells interact with the components of TME, which is beneficial for their survival, ultimately causing the formation of immunosuppressive and high-metabolism TME. In the process, transforming growth factor-β (TGF-β), as a pivotal cytokine in the TME, controls various cells’ fates and influences numerous metabolic pathways, including inhibiting immune cells to infiltrate the tumors, suppressing the activation of anti-tumor immune cells, facilitating more immunosuppressive cells, enhancing glucose and glutamine metabolism, dysregulating bone metabolism and so on. Thus, we consider TGF-β as the tumor promoter. However, in healthy cells and the early stage of tumors, it functions as a tumor suppressor. Due to the effect of context dependence, TGF-β has dual roles in TME, which attracts us to further explore whether targeting it can overcome obstacles in the treatment of MM by regulating the progression of myeloma, molecular mechanisms of drug resistance, and various signaling pathways in the immune and metabolic microenvironment. In this review, we predominantly discuss that TGF-β promotes the development of MM by influencing immunity and metabolism.
“How I would like AI used for my imaging”: children and young persons’ perspectives
Authors: Lee Lauren , Salami Raimat Korede , Martin Helena , Shantharam Lavanhya , Thomas Kate , Ashworth Emily , Allan Emma , Yung Ka-Wai , Pauling Cato , Leyden Deirdre , Arthurs Owen J. , Shelmerdine Susan Cheng
Published: June 2024

Objectives

Artificial intelligence (AI) tools are becoming more available in modern healthcare, particularly in radiology, although less attention has been paid to applications for children and young people. In the development of these, it is critical their views are heard.

Materials and methods

A national, online survey was publicised to UK schools, universities and charity partners encouraging any child or young adult to participate. The survey was “live” for one year (June 2022 to 2023). Questions about views of AI in general, and in specific circumstances (e.g. bone fractures) were asked.

Results

One hundred and seventy-one eligible responses were received, with a mean age of 19 years (6–23 years) with representation across all 4 UK nations. Most respondents agreed or strongly agreed they wanted to know the accuracy of an AI tool that was being used (122/171, 71.3%), that accuracy was more important than speed (113/171, 66.1%), and that AI should be used with human oversight (110/171, 64.3%). Many respondents (73/171, 42.7%) felt AI would be more accurate at finding problems on bone X-rays than humans, with almost all respondents who had sustained a missed fracture strongly agreeing with that sentiment (12/14, 85.7%).

Conclusions

Children and young people in our survey had positive views regarding AI, and felt it should be integrated into modern healthcare, but expressed a preference for a “medical professional in the loop” and accuracy of findings over speed. Key themes regarding information on AI performance and governance were raised and should be considered prior to future AI implementation for paediatric healthcare.

Clinical relevance statement

Artificial intelligence (AI) integration into clinical practice must consider all stakeholders, especially paediatric patients who have largely been ignored. Children and young people favour AI involvement with human oversight, seek assurances for safety, accuracy, and clear accountability in case of failures.

Key Points

Paediatric patient’s needs and voices are often overlooked in AI tool design and deployment.

Children and young people approved of AI, if paired with human oversight and reliability.

Children and young people are stakeholders for developing and deploying AI tools in paediatrics.
Preoperative proteinuria correlates with renal function after partial nephrectomy for renal cell carcinoma
Authors: Nicolazzini Michele , Palumbo Carlotta , Porté Francesca , Bondonno Gianmarco , De Angelis Paolo , Del Galdo Maria Teresa , Volpe Alessandro
Published: June 2024

Purpose

Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal function after partial nephrectomy (PN).

Methods

We retrospectively reviewed our records of patients with a single malignant renal mass who underwent PN between 2000 and 2021. Patients with data on preoperative proteinuria were included. Baseline characteristics and eGFR differences over time between patients with and without proteinuria were evaluated. Univariate and multivariable logistic regression models (LRM) tested for presence of CKDIII or higher at 12-month and at last follow-up.

Results

Two hundred ninety-five patients were included. Twenty-two of them had preoperative proteinuria. No differences of age, smoking status, hypertension or diabetes, tumor size and use of ischemia were observed. Patients with proteinuria had a higher rate of CKD-III at baseline. At a median follow-up of 46.5 months (IQR 19–82), 117 patients developed de novo CKD-III, without differences in the two groups. No differences in decline in eGFR were observed. At univariate LRM, predictors of CKD-III at 12 months after PN were preoperative proteinuria (OR 3.2, 95%CI 1.4–7.8, p = 0.005), age and baseline eGFR, while predictors of CKD-III at last follow-up were age and baseline eGFR. At multivariable LRM, only baseline eGFR predicted CKD-III at 12-month and at last-follow-up.

Conclusions

Preoperative eGFR is the only independent predictor of long-term renal function after PN. Preoperative proteinuria correlates with renal function at 12 months. Proteinuria should be assessed before PN to identify patients at higher risk of renal functional deterioration in the 12 months following PN.
HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion
Authors: Liu Yu , Wu Ruifang , Li Changzhong , Duan Lvfang , Wei Lihui , Li Ruizhen
Published: June 2024

Purpose

We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL).

Methods

Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48–72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2.

Results

The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT.

Conclusions

HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.
The influence of cooling on biomechanical time since death estimations using ovine brain tissue
Authors: Zwirner Johann , Devananthan Pavithran , Docherty Paul D. , Ondruschka Benjamin , Kabaliuk Natalia
Published: June 2024

The significance of biomechanical analyses for forensic time since death estimations has recently been demonstrated. Previous biomechanical analyses successfully discriminated post-mortem brain tissue from tissue with a post-mortem interval of at least one day when held at 20 °C. However, the practical utility of such analyses beyond day one at 20 °C was limited. This study investigates the storage, loss, and complex shear modulus of various brain regions in sheep stored at 4 °C in 24-hour intervals over four days post-mortem using rheometry tests. The aim is to identify the critical biomechanical tissue property values to predict post-mortem time and assess the temperature sensitivity of the rheometry method by comparing results to recent findings at 20 °C. Thirty sheep brains were examined, including the frontal lobe, parietal lobe, anterior and posterior deep brain, superior colliculi, pons, medulla, and cerebellum. Rheometry tests were conducted, and receiver operator characteristic analyses were employed to establish cut-off values. At 4 °C storage, all investigated biomechanical properties of the examined brain regions remained stable for at least one day post-mortem. Using cerebellar samples stored at 4 °C, a post-mortem interval of at least two days could be determined with excellent diagnostic ability. Complex shear modulus values below 1435 Pa or storage modulus values below 1313 Pa allowed prediction of two or more days post-mortem. Comparisons between 4 °C and 20 °C revealed brain region-specific results. For instance, the complex shear moduli of the anterior deep brain at 4 °C were significantly higher on all individual testing days when compared to 20 °C. In contrast, the combined medulla and pons samples were similar on each day. Rheometry testing of brain tissue consistently stored at 4 °C since death proved valuable for forensic time since death estimations starting from two days after death.
Predicting daily recovery during long-term endurance training using machine learning analysis
Authors: Rothschild Jeffrey A. , Stewart Tom , Kilding Andrew E. , Plews Daniel J.
Published: June 2024

Purpose

The aim of this study was to determine if machine learning models could predict the perceived morning recovery status (AM PRS) and daily change in heart rate variability (HRV change) of endurance athletes based on training, dietary intake, sleep, HRV, and subjective well-being measures.

Methods

Self-selected nutrition intake, exercise training, sleep habits, HRV, and subjective well-being of 43 endurance athletes ranging from professional to recreationally trained were monitored daily for 12 weeks (3572 days of tracking). Global and individualized models were constructed using machine learning techniques, with the single best algorithm chosen for each model. The model performance was compared with a baseline intercept-only model.

Results

Prediction error (root mean square error [RMSE]) was lower than baseline for the group models (11.8 vs. 14.1 and 0.22 vs. 0.29 for AM PRS and HRV change, respectively). At the individual level, prediction accuracy outperformed the baseline model but varied greatly across participants (RMSE range 5.5–23.6 and 0.05–0.44 for AM PRS and HRV change, respectively).

Conclusion

At the group level, daily recovery measures can be predicted based on commonly measured variables, with a small subset of variables providing most of the predictive power. However, at the individual level, the key variables may vary, and additional data may be needed to improve the prediction accuracy.
Status quo of operative training in emergency surgery in Germany – results of a survey
Authors: Wachter N. , Güsgen C. , Geis C. , Penzkofer L.S. , Oldhafer K. , Willms A.G. , Huber Tobias
Published: June 2024

Background

Emergencies and emergency surgeries are a central part of everyday surgical care in Germany. However, it is unclear how emergency surgery is practically trained in clinics on a daily basis and what training concept is underlying. Therefore, the aim of this survey study was to capture the status quo of emergency surgical training of German general and visceral surgeons.

Methods

The members of the German Society for General and Visceral Surgery were surveyed online (n = 5281). The questionnaire included demographic data and expertise in surgery and assistance in emergency surgery regarding common emergency surgical operations. In addition, further training measures in emergency surgery and their support by employers were queried.

Results

Only complete questionnaires (n = 184, response rate 3.5%) were included in the analysis. Most participants were in training (n = 69; 38%), followed by senior physicians (n = 52; 29%), specialists (n = 31; 17%) and chief physicians (n = 30; 17%). 64% of the participants were employed at university hospitals or maximum care hospitals. Regarding further training opportunities, in-clinic shock room training was most frequently used. Outside of their own clinic, the ATLS course was most frequently mentioned. Operations for cholecystitis and appendicitis as well as emergency stoma procedures are the most common emergency procedures. There was a strong difference in the frequency of operated cases depending on the level of training. For operations to treat acute abdominal traumas (hemostasis of liver and spleen, packing) as well as outside of visceral surgery, only low competence was reported. Over 90% of survey participants consider emergency surgery to be an indispensable core competence. Neither in the old (76%) nor in the new training regulations (47%) is emergency surgery adequately represented according to the participants’ assessment. There was a significantly lower prevalence of the “sub-steps concept” in emergency surgery at 38% compared to elective surgery (44%). Important elements of imparting skills in emergency surgery are simulation and courses as well as operative sub-steps, according to the majority of survey participants.

Conclusion

The results show that general and visceral surgeons in Germany are introduced to emergency surgery too little structured during further training and at specialist level. The survey participants had, as expected, hardly any experience in emergency surgery outside of visceral surgery but surprisingly also little experience in visceral surgical trauma care. There is a need to discuss the future organization of emergency surgical training. Adequate simulation structures and extracurricular courses could contribute to an improvement in this respect.
Lysozyme: an endogenous antimicrobial protein with potent activity against extracellular, but not intracellular Mycobacterium tuberculosis
Authors: Maier Felix Immanuel , Klinger David , Grieshober Mark , Noschka Reiner , Rodriguez Armando , Wiese Sebastian , Forssmann Wolf-Georg , Ständker Ludger , Stenger Steffen
Published: June 2024

Endogenous antimicrobial peptides (AMPs) play a key role in the host defense against pathogens. AMPs attack pathogens preferentially at the site of entry to prevent invasive infection. Mycobacterium tuberculosis (Mtb) enters its host via the airways. AMPs released into the airways are therefore likely candidates to contribute to the clearance of Mtb immediately after infection. Since lysozyme is detectable in airway secretions, we evaluated its antimicrobial activity against Mtb. We demonstrate that lysozyme inhibits the growth of extracellular Mtb, including isoniazid-resistant strains. Lysozyme also inhibited the growth of non-tuberculous mycobacteria. Even though lysozyme entered Mtb-infected human macrophages and co-localized with the pathogen we did not observe antimicrobial activity. This observation was unlikely related to the large size of lysozyme (14.74 kDa) because a smaller lysozyme-derived peptide also co-localized with Mtb without affecting the viability. To evaluate whether the activity of lysozyme against extracellular Mtb could be relevant in vivo, we incubated Mtb with fractions of human serum and screened for antimicrobial activity. After several rounds of sub-fractionation, we identified a highly active fraction-component as lysozyme by mass spectrometry. In summary, our results identify lysozyme as an antimycobacterial protein that is detectable as an active compound in human serum. Our results demonstrate that the activity of AMPs against extracellular bacilli does not predict efficacy against intracellular pathogens despite co-localization within the macrophage. Ongoing experiments are designed to unravel peptide modifications that occur in the intracellular space and interfere with the deleterious activity of lysozyme in the extracellular environment.
Laser therapy for treating cleft lip or/and palate scarring—a systematic review and meta-analysis
Authors: Sun Yixin , Li Ziming , Qi Xiaoyu , Wang Binghan , Yu Nanze , Huang Jiuzuo , Ting Wenyun , Long Xiao
Published: June 2024

This review aims to assess the efficacy and safety of laser therapy in managing scars resulting from cleft lip and/or palate (CL/P) repair surgeries, as well as to determine the optimal timing for intervention. A systematic search was conducted across four databases using a predefined search strategy. Studies included were randomized controlled trials, non-randomized studies, and case series focusing on laser therapy for CL/P scars. Data extraction and analysis were performed using Revman Software. A total of two randomized controlled trials, four non-randomized studies, and three case series were included in the analysis. The fractional CO2 laser was the most commonly utilized type of laser. Following laser therapy, there was a significant decrease in Vancouver Scar Scale (VSS) scores by 4.05 (95% CI, 2.10–5.99). Meta-analysis revealed that laser treatment groups exhibited a significantly lower mean VSS score (1.3; 95% CI, 0.02–2.67) compared to control groups. Moreover, initiating laser therapy intervention at one month postoperatively resulted in a significantly lower VSS score compared to initiation at three months postoperatively (difference of 1.70; 95% CI, 1.33–2.08). No severe complications were reported. Laser therapy demonstrates effectiveness and safety in improving CL/P scars, with earlier intervention yielding greater benefits.
Trajectory Tracking Control of Fixed-Wing Hybrid Aerial Underwater Vehicle Subject to Wind and Wave Disturbances
Authors: Li Junping , Jin Yufei , Hu Rui , Bai Yulin , Lu Di , Zeng Zheng , Lian Lian
Published: June 2024

The hybrid aerial underwater vehicle (HAUV) could operate in the air and underwater might provide a great convenience for aerial and underwater exploration, and the fixed-wing HAUV (FHAUV) has time, space and cost advantages in future large-scale applications, while the large difference between the aerial and underwater environments is a challenge to control, especially in the air/water transition. However, for FHAUV control, there is a lack of research on phenomena or problems caused by large changes in the air/water transition. In addition, the effects of wind, wave, other factors and conditions on motion control are not investigated. This paper presents the first control study on the above issues. The motion model of FHAUV is developed, with the effects of wind and wave disturbances. Then, this paper improves a cascade gain scheduling (CGS) PID for different media environments (air and water) and proposes a cascade state feedback (CSF) control strategy to address the convergence problem of FHAUV control caused by large speed change in the air/water transition. In the comparisons of the two control schemes in various tracking cases including trajectory slopes, reference speeds, wind and wave disturbances, CSF has a better control effect, convergence rate and robustness; the key factors and conditions of the air/water transition are investigated, the critical relations and feasible domains of the trajectory slopes and reference speeds that the FHAUV must meet to successfully exit the water and enter the air are obtained, the critical slope decreases as the reference speed increases, and the feasible domain of CSF is larger than that of CGS, revealing that CSF is superior than CGS for exiting the water.
The digital operational resilience act: challenges and some reflections on the adequacy of Europe’s architecture for financial supervision
Authors: Buttigieg Christopher P. , Zimmermann Beatriz Brunelli
Published: June 2024

The paper critically analyses the Digital Operational Resilience Act (DORA) within the European Union (EU) with respect to challenges such as supervision and the oversight framework coordination. It delves into the adequacy of the European System of Financial Supervision (ESFS) in ensuring compliance with this regulation, highlighting issues of fragmented supervision at national level and inconsistent approaches. The main argument suggests that while the DORA Regulation is a positive step for harmonising digital operational resilience regulation, it brings about challenges in supervisory convergence and cooperation due to the existing fragmented supervisory architecture. The authors propose potential solutions like a more centralised supervision model to address these challenges. The paper follows a structured format with an overview of the DORA Regulation, discussion on identified challenges, and a concluding section.
Human Microglia–Like Cells Differentiated from Monocytes with GM-CSF and IL-34 Show Phagocytosis of α-Synuclein Aggregates and C/EBPβ-Dependent Proinflammatory Activation
Authors: Llaves-López Andrea , Micoli Elia , Belmonte-Mateos Carla , Aguilar Gerard , Alba Clara , Marsal Anais , Pulido-Salgado Marta , Rabaneda-Lombarte Neus , Solà Carme , Serratosa Joan , Vidal-Taboada Jose M. , Saura Josep
Published: June 2024

Microglia, the main resident immune cells in the central nervous system, are implicated in the pathogenesis of various neurological disorders. Much of our knowledge on microglial biology was obtained using rodent microglial cultures. To understand the role of microglia in human disease, reliable in vitro models of human microglia are necessary. Monocyte-derived microglia-like cells (MDMi) are a promising approach. This study aimed to characterize MDMi cells generated from adult human monocytes using granulocyte–macrophage colony-stimulating factor and interleukin-34. To this end, 49 independent cultures of MDMI were prepared, and various methodological and functional studies were performed. We show that with this protocol, adult human monocytes develop into microglia-like cells, a coating is unnecessary, and high cell density seeding is preferable. When compared to monocytes, MDMi upregulate the expression of many, but not all, microglial markers, indicating that, although these cells display a microglia-like phenotype, they cannot be considered bona fide human microglia. At the functional level, MDMi phagocytose α-synuclein aggregates and responds to lipopolysaccharide (LPS) by nuclear translocation of the transcription factor nuclear factor-kappaB (NFkappaB) and the upregulation of proinflammatory genes. Finally, a long-lasting silencing of the transcription factor CCAAT/enhancer protein β (C/EBPβ) was achieved by small interfering RNA, resulting in the subsequent downregulation of proinflammatory genes. This supports the hypothesis that C/EBPβ plays a key role in proinflammatory gene program activation in human microglia. Altogether, this study sheds new light on the properties of MDMi cells and supports these cells as a promising in vitro model for studying adult human microglia–like cells.
Mapping the Behavioral Signatures of Shank3b Mice in Both Sexes
Authors: Liu Jingjing , Ye Jialin , Ji Chunyuan , Ren Wenting , He Youwei , Xu Fuqiang , Wang Feng
Published: June 2024

Autism spectrum disorders (ASD) are characterized by social and repetitive abnormalities. Although the ASD mouse model with Shank3b mutations is widely used in ASD research, the behavioral phenotype of this model has not been fully elucidated. Here, a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice. It was found that both sexes replicated the core and accompanied symptoms of ASD, with significant sex differences. Further, Shank3b heterozygous knockout mice exhibited distinct autistic behaviors, that were significantly different from those those observed in the wild type and homozygous knockout groups. Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models, which are more clinically relevant in autistic studies.
Principles of EU law in climate litigation
Authors: Colombo Esmeralda
Published: June 2024

The present contribution questions the role of principles of EU law in climate litigation. Notwithstanding their importance within the EU general regulatory framework, their operationalisation in climate litigation is underexplored. To appreciate EU principles in the context of climate change litigation, this paper positions them within the scope and dynamics of climate change litigation worldwide. Secondly, with this background, the analysis develops as a case law review on the emerging role of the precautionary principle, intergenerational equity, and the minimum harmonisation principle in the climate litigation. To date, five relevant climate lawsuits have unfolded before the courts of EU Member States, which allows for canvassing the content, status, and significance of the principles under examination with concrete examples of the climate lawsuits where these principles have been applied. In this regard, the paper finds that courts in Member States have steadily provided protection of the climate and future generations through rights-based arguments supported by principles. In this context, domestic courts seem to be filling the normative gap left by the CJEU by interpreting fundamental rights in relation to EU environmental principles in what I conceptualise as “the rights turn through principles.” As a final point, the paper concludes with the prospective development of EU principles in the EU legal order and beyond, possibly enabling comparisons with other jurisdictions.
Bisexual Discrimination, Internalized Binegativity and their Impact on Mental Health
Authors: Velasco Judith , Miranda-Tena Andrea , Sanmartín Francisco J.
Published: June 2024

Introduction

Bisexual individuals experience discrimination both from heterosexual individuals and from the Lesbian and Gay (LG) community. This double discrimination affects their mental health. This study aimed to explore the relationship between binegativity (from heterosexual and LB individuals) and internalized binegativity and symptoms of depression and anxiety, as well as the mediating role of social support. The second purpose was to explore whether these variables could predict the symptoms of depression and anxiety.

Methods

A sample of 110 bisexual individuals (77.3% cisgender women, Mage = 25.2) completed self-report measures.

Results

Most participants reported being discriminated against by heterosexual (93.2%) and LG (81.8%) individuals. However, they perceived and experienced higher discrimination from heterosexual people. The majority experienced internalized binegativity. As hypothesized, heterosexual discrimination predicted depressive and anxiety symptoms. Contrary to expectations, discrimination from the LG community and internalized binegativity did not predict symptoms, although bivariate correlations showed a positive relationship. Social support was a moderator of symptoms of depression, but not of anxiety.

Conclusions

These findings highlight the impact of binegativity on the mental health of bisexual individuals and the importance of social support.

Policy implications

Our results provide practitioners and policymakers with evidence of the effects of discrimination experienced by bisexual individuals. Educational campaigns and public awareness programs are needed to foster a more inclusive and accepting society.
Classification of Diffusion Constants of Transmitter and Receiver and Distance Between Them Using Mobile Molecular Communication via Diffusion Model
Authors: Er Mehmet Bilal , Isik Ibrahim , Kuran Umut , Isik Esme
Published: June 2024

Molecular communication (MC) holds promise for enabling communication in scenarios where traditional wireless methods may be impractical or ineffective, offering unique capabilities for a range of applications in both natural and engineered systems. In this research, a novel approach to MC is explored, diverging from the standard use of stationary transmitter and receiver models typically found in the field. The study introduces a dynamic MC model, where both the transmitter and receiver are mobile within a diffusion environment. This model operates using a 5-bit system. The key finding is that the mobility of these nanodevices alters their distance, which in turn impacts the likelihood of molecule reception at the receiver. The study employs deep learning techniques, specifically a combination of Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM) networks, to categorize the mobility patterns of the receiver (Rx) and transmitter (Tx). By analyzing various mobility rates (Drx and Dtx) and distances between the Tx and Rx, the research successfully identifies the most efficient mobile MC model in terms of molecule reception rates. The use of Linear Support Vector Machine alongside the CNN and LSTM hybrid feature vector resulted in an 87.68% accuracy in predicting diffusion coefficients. Moreover, using a Cubic Support Vector with the same hybrid feature vector, the study achieved an 88.09% accuracy in estimating the distance between the transmitter and receiver. The study concludes that an increase in the mobilities of Rx and Tx correlates with a higher rate of molecule reception.
The confluence of attitudes towards mathematics and pedagogical practice: evaluating the use of mathematical manipulatives
Authors: Quane Kate
Published: June 2024

The use of manipulatives to develop conceptual understanding is a prevalent practice in many mathematical learning experiences, particularly in the early years of schooling. From primary student perspectives, our understanding of the impact of manipulatives in mathematics education on students’ attitudes is limited. This study evaluates the impact of mathematical manipulatives on Young Children’s Attitudes Towards Mathematics (YCATM) by examining children’s drawings, as well as their written and verbal descriptions of their drawings from 106 year 2 and year 3 students. Classroom observations were conducted to investigate how attitudes towards mathematics are enacted during mathematical learning experiences. The modified three-dimensional model of attitude (MTMA) and Bruner’s experiential stages were used to investigate how manipulatives influence YCATM. Data analyses used systematic, numerical coding, and thematic and comparative approaches, employing inductive, deductive, and anticipatory coding for data from both lesson and non-lesson contexts. The findings suggest that young children enjoyed using manipulatives, contributing to their vision of mathematics and perceived competence. However, the transition between enactive, iconic, and symbolic experiences can contribute to the formation of negative attitudes. The present study also emphasizes the importance of context, content, and familiarity with the use of manipulatives.
On Darboux theorems for geometric structures induced by closed forms
Authors: Gràcia Xavier , de Lucas Javier , Rivas Xavier , Román-Roy Narciso
Published: June 2024

This work reviews the classical Darboux theorem for symplectic, presymplectic, and cosymplectic manifolds (which are used to describe mechanical systems), as well as certain cases of multisymplectic manifolds, while extends the Darboux theorem in new ways to k-symplectic and k-cosymplectic manifolds (all these structures appear in the geometric formulation of first-order classical field theories). Moreover, we discuss the existence of Darboux theorems for classes of precosymplectic, k-presymplectic, k-precosymplectic, and premultisymplectic manifolds, which are the geometrical structures underlying some kinds of singular field theories, i.e. with locally non-invertible Legendre maps. Approaches to Darboux theorems based on flat connections associated with geometric structures are given, while new results on polarisations for (k-)(pre)(co)symplectic structures arise.