bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling reliable usability assessment and comparative analysis of medical software: a comprehensive framework for multimodal biomedical imaging platforms
Authors: Denisova Elena , Tiribilli Eleonora , Luschi Alessio , Francia Piergiorgio , Manetti Leonardo , Bocchi Leonardo , Iadanza Ernesto
Published: May 2024

Purpose

A literature review reveals that, at the moment, all usability tests for Software as a Medical Device (SaMD) are designed in compliance with international standards but it also reveals a lack of formalization in the implementation and administration of such usability tests, which prevents the comparison of results from different tests for the same class of SaMD. This study aims to provide a reproducible usability testing framework for SaMD to establish a standardized protocol which can ensure repeatability and comparisons of similar SaMD for the visualization of medical images and data.

Methods

The devised protocol aligns with international standards and literature recommendations for usability and human factors engineering. It encompasses participant selection, testing environments, equipment setup for various testing methods (HDMI vs. wireless), and hardware interfaces (keyboard/mouse vs. touchscreen), as well as the roles of the required testers. The protocol consists of two distinct sections: exploratory tasks and specific scenarios, to assess software functions and real-life tasks, respectively. Effectiveness and efficiency are evaluated using video analysis and a custom Stopwatch software, while user satisfaction is measured through post-test questionnaires.

Results

The usability testing protocol was applied to a Multimodal Biomedical Imaging Platform All-in-One software developed by Imaginalis S.r.l. (Sesto Fiorentino, Italy) for validation. The results of the usability testing protocol applied to the case-study software demonstrate good values of software’s effectiveness and efficiency, along with user satisfaction supporting the prior heuristic evaluation. The outcomes confirm the robustness, applicability, and reproducibility of the usability testing protocol, aligning with best practices.

Conclusions

The proposed usability testing framework enables reliable usability assessment and comparative analysis of medical software. Furthermore, the obtained results can serve as a reference for assessing other biomedical imaging platforms under development or ready for release.
Carbon ion radiotherapy in gynaecological oncology: where we are and where we are headed
Authors: Barcellini Amelia , Charalampopoulou Alexandra , Franzetti Jessica , Locati Laura Deborah , Orlandi Ester
Published: May 2024

Purpose

In the present brief report, the authors summarized the data on the use of carbon ion radiotherapy in gynaecological malignancies starting from the preclinical evidence to move forward the clinically available literature and hence focusing on the possible future application directions.

Methods

This is a short report of the published studies on the role of carbon ion radiotherapy in the treatment of gynaecological malignancies.

Results

The use of carbon ion radiotherapy in rare and radioresistant gynaecological tumors is supported by preclinical and clinical data. In particular, carbon ion radiotherapy appears to be safe and effective in the management of cervical adenocarcinomas, unresectable endometrial cancers, mucosal melanomas of the lower genital tract and vulvar adenoid cystic carcinomas. Moreover, considering the dosimetric characteristics, carbon ions are suitable for recurrent disease in the pelvis. Prospective and phase II trials on gynaecological melanomas and pelvic relapses after radiotherapy are currently ongoing. The future study directions might be the oligometastatic diseases and the oncofertility.

Conclusions

More and more growing preclinical and clinical evidence supports the use of carbon ion radiotherapy in gynaecological oncology. Strong and multidisciplinary collaborations at national and international levels are desirable to better understand the therapeutic and organizational benefits of this new technology.
Something Out of Nothing? The Influence of Double-Zero Studies in Meta-analysis of Adverse Events in Clinical Trials
Authors: Fan Zhaohu , Liu Dungang , Chen Yuejie , Zhang Nanhua
Published: May 2024

In addition to clinical efficacy, safety is another important outcome to assess in randomized controlled trials. It focuses on the occurrence of adverse events, such as stroke, deaths, and other rare events. Because of the low or very low rates of observing adverse events, meta-analysis is often used to pooled together evidence from dozens or even hundreds of similar clinical trials to strengthen inference. A well-known issue in rare-event meta-analysis is that some or even majority of the available studies may observe zero events in both the treatment and control groups. The influence of these so-called double-zero studies has been researched in the literature, which nevertheless focuses on reaching a dichotomous conclusion—whether or not double-zero studies should be included in the analysis. It has not been addressed when and how they contribute to inference, especially for the odds ratio. This paper fills this gap using comparative analysis of real and simulated data sets. We find that a double-zero study contributes to the odds ratio inference through its sample sizes in the two arms. When a double-zero study has an unequal allocation of patients in its two arms, it may contain non-ignorable information. Exclusion of these studies, if taking a significant proportion of the study cohort, may result in inflated type I error, deteriorated testing power, and increased estimation bias.
Is It Worth Investing in Tokens? Investment Performance of Digital Tokens in Financial and Axiological Contexts
Authors: Nowak Karolina Anna , Wiśniewski Marcin , Litwiński Michał
Published: May 2024

The paper focuses on financial and axiological aspects of the new instrument in the digital economy, such as digital tokens (DTs). The purpose of the article is to examine the investment performance of certain types of DTs. We suggest a categorisation of DTs according to the types of assets that they represent and analyse them in terms of profitability, risk, and effectiveness. The investment performance of different types of DTs was compared with stock market indices and commodity prices. The empirical source of information is data from the coinpaprika platform from January 2018 to July 2022. It occurs that DTs demonstrate, on average, lower investment performance than traditional instruments. However, there is a wide group of the former that can be included in the portfolio as their investment performance is higher than the one represented by stock market assets. Our contribution comprises, first, the extension of existing research on tokenization and tokens to include the investment aspect. Second, we develop and apply the original proposal of DT classification, which takes into account the hitherto neglected aspect of worldview valuation of a given DT type by market participants. Finally, we assess the investment performance of DTs (both in terms of our proposed classification and in the context of stock market indices). We also specify recommendations for investors.
Ensemble learning-based structural health monitoring of a bridge using an interferometric radar system
Authors: Yaghoubzadehfard Ali , Lumantarna Elisa , Herath Nilupa , Sofi Massoud , Rad Mehmet
Published: May 2024

Due to the increase in population, urbanisation, transportation development, and the aging of existing bridges, there is a growing need for new and rapid structural health monitoring (SHM) of bridges. To address this challenge, a method that stands out is the use of an interferometric radar system-based device, specifically Image by Interferometric Survey-Frequency for structures (IBIS-FS). Known for its portability and non-intrusive operation, IBIS-FS does not require direct contact with the bridge. This study utilised IBIS-FS to capture a pedestrian bridge’s natural frequencies and mode shapes. The data obtained were found to be consistent with results from finite element models, demonstrating the reliability of IBIS-FS in capturing modal parameters. Building upon this foundation, the study then explores the application of advanced ensemble-based machine-learning techniques. By leveraging the data acquired from IBIS-FS, algorithms such as Random Forest, Gradient-boosted Decision Trees (GBDT), and Extreme Gradient Boosting (XGBoost) are used for bridge damage detection. These machine-learning (ML) techniques are suited to analyse the incomplete modal parameters of bridges, as captured by IBIS-FS. The study focuses on using these algorithms to interpret the changes in modal parameters, specifically identifying damage as a reduction in the stiffness of elements. This approach allows for a comprehensive analysis, where the modal parameters, including mode shapes and natural frequencies altered by varying noise levels, are fed as input to the models. It was observed that all three ML methods, with Random Forest in particular, can effectively identify the location and severity of damage, demonstrating an efficient training process. The robustness of GBDT and XGBoost in handling complex data sets also shows great promise for their application in bridge damage detection. Collectively, these results underscore the potential of combining advanced ML techniques like Random Forest, GBDT, and XGBoost with the data acquired from IBIS-FS.
Filling the plane with squares of harmonic areas
Authors: Januszewski Janusz , Zielonka Łukasz
Published: May 2024

Some filling the plane with squares of areas$$1, 1/2, 1/3, 1/4, \ldots $$1,1/2,1/3,1/4,…is presented.
Antiviral and anti-inflammatory activities of chemical constituents from twigs of Mosla chinensis Maxim
Authors: Feng Shi-Yan , Jiang Na , Yang Jia-Ying , Yang Lin-Yao , Du Jiang-Chao , Chen Xuan-Qin , Liu Dan , Li Rong-Tao , Zhong Jin-Dong
Published: May 2024

Seven undescribed compounds, including three flavones (1–3), one phenylpropanoid (19), three monoaromatic hydrocarbons (27–29), were isolated from the twigs of Mosla chinensis Maxim together with twenty-eight known compounds. The structures were characterized by HRESIMS, 1D and 2D NMR, and ECD spectroscopic techniques. Compound 20 displayed the most significant activity against A/WSN/33/2009 (H1N1) virus (IC50 = 20.47 μM) compared to the positive control oseltamivir (IC50 = 6.85 µM). Further research on the anti-influenza mechanism showed that compound 20 could bind to H1N1 virus surface antigen HA1 and inhibit the early attachment stage of the virus. Furthermore, compounds 9, 22, 23, and 25 displayed moderate inhibitory effects on the NO expression in LPS inducing Raw 264.7 cells with IC50 values of 22.78, 20.47, 27.66, and 30.14 µM, respectively.

Graphical Abstract
Effect of Particle Size and Starch Gelatinization on the Mechanical and Metallurgical Performance of Jarosite Plus Blast Furnace Sludge Self-Reducing Briquettes
Authors: Dall’Osto G. , Mombelli D. , Trombetta V. , Mapelli C.
Published: May 2024

Jarosite and blast furnace sludge (BFS) are two of the main wastes from hydrometallurgical zinc production and iron production by blast furnace, respectively. Jarosite is a hazardous material that can, however, be reused in the steel industry after the recovering of the iron contained within it through carbothermal reduction in which BFS is exploited as a reducing agent. Yet, both wastes have a powdery nature that makes it necessary to agglomerate them for industrial use. On the other hand, despite the advantages of producing a self-reducing product, the particle size of the starting powders and the level of gelatinization of the binder could play a crucial role on the mechanical and metallurgical performance and, consequently, on the industrial applicability of the briquettes. Accordingly, two powder particle sizes (very fine sand vs. coarse silt) and three degree of corn starch binder retrogradation (10%, 30% and non-gelatinized starch) were used to produce briquettes, and their influence was studied by experimental and statistical investigation. The results showed that gelatinization plays the main role on the mechanical properties of briquettes, while particle size affects both density and reduction behavior; in particular, although all the mixtures were able to recover iron at 950 °C the most optimal mixture were obtained by using a granulometry of 63–125 µm for jarosite and less than 63 µm for BFS, while the local maximum of mechanical performance was obtained for a 30% starch retrogradation level.

Graphical Abstract
Fused granulate fabrication of injection molding inserts from high-performance ULTEM 9085™ thermoplastic for cosmetic packaging industry
Authors: Curmi Albert , Rochman Arif
Published: May 2024

RTIM refers to the integration of rapid tooling (RT) using additive manufacturing (AM) with injection molding (IM). Due to the use of raw material (pellet), screw extrusion, fused granulate fabrication (FGF) allows for a cost-effective and versatile production of RTIM inserts especially compared to other material extrusion (MEX) AM processes, such as fused filament fabrication (FFF). This study 3D printed RTIM inserts out of high-performance thermoplastic polyetherimide (PEI) (ULTEM 9085) in granular form, using an in-house developed FGF system. A cosmetic compact was used as a case study part with a simplified design. A dynamic mechanical analysis (DMA) conducted on FGF ULTEM 9085 demonstrated that the strength of the inserts is sustained up to 140 °C, which suits injection molding using polypropylene (PP). Optical profilometry of the FGF 3D printed RTIM inserts demonstrated that when using a 0.4 mm nozzle, the flat surfaces produced had microscopic gaps larger than 10–1 mm. These gaps are sufficiently large so that melt of low viscosity polymer is able to flow through, which leads to undesired part flash. The IM experiments confirmed that the inserts were capable of producing PP parts but with the predicted flash. Simulated part deflection differed both on geometry and magnitude from the actual deflection measured by optical profilometry. A total of 36 prototype parts were produced before the inserts failed due to poor inter-layer bond strength. FGF RTIM using ULTEM 9085 is deemed suitable for prototype part production. Improving the inter-layer bond strength and decreasing part complexity could increase the number of parts produced.
A harmonic property of right invariant priors
Authors: Sei Tomonari , Komaki Fumiyasu
Published: May 2024

It is shown that, on any Lie group, the density ratio of the right invariant measure to the left invariant measure is harmonic with respect to the left invariant Riemannian metric. This result is applied to the Bayesian prediction theory on group invariant statistical models. A method of constructing Bayesian prior distributions that asymptotically dominate the right invariant priors is provided.
A solution to the only one object problem with dissolution rules
Authors: Caselmann Julien , Orellana-Martín David
Published: May 2024

In the framework of membrane computing, (non-)uniform families of recognizer membrane systems are usually defined to solve abstract decision problems. In this sense, the use of finite resources for each member of the family makes the difference with respect to Turing machines solving these problems. While keeping the finite nature of these systems, it is interesting to know which type of problems can be solved by means of a single membrane system. For this purpose, the complexity class $$\textbf{PMC}^{1p}_{\mathcal {R}}$$

PMC
R

1
p

was defined as the class of problems that can be solved by means of a single membrane system in polynomial time. Due to the polynomial-time encoding of the input, at least all the problems from P can be solved with a trivial system. To go below P, the class $$\textbf{PMC}^{1f}_{\mathcal {R}}$$

PMC
R

1
f

restricts the definition of this encoding. In this work, we study the capability of different types of membrane systems to solve the problem, while having the encoding restriction.
Potential enhancements in the photocatalytic activity of the anatase 001 surface by adding cerium impurity
Authors: Jiménez Gladys Casiano , Alcalá Varilla Luis A. , Torres Hoyos Francisco
Published: May 2024

This research investigates the structural and electronic properties of titanium dioxide ($$ TiO_2 $$

T
i

O
2

) surfaces with the addition of cerium (Ce) impurities using first principles calculations within the framework of density functional theory, employing the pseudopotential method and the computational package Quantum ESPRESSO. Density of states (DOS) calculations reveal that the clean surface exhibits semiconductor behavior. In contrast, the titanium dioxide surface with Ce impurities on the fifth layer generates intermediate states within the energy band gap, resulting in a reduction in the band, with an intraband energy gap of 0.7882 eV induced. Moreover, the inclusion of a Ce atom on the fourth layer of the surface results it is observed that the surface an important characteristic is the appearance of intermediate states in the band gap, which are close to the valence band with a magnetic moment of 0.91 $$ \mu \beta /cell $$

μ
β
/
c
e
l
l

. The ntraband gap can enhance the utilization of the visible spectrum. Additionally, the Ce impurity on the $$ TiO_2 $$

T
i

O
2

surface could promote greater photocatalytic activity in pollutant degradation and increase the oxidative capacity of titanium dioxide.
Engagement of modified heat and mass fluxes on thermally radiated boundary layer flow past over a stretched sheet via OHAM analysis
Authors: Sohail Muhammad , Rafique Esha , Singh Abha , Tulu Ayele
Published: May 2024

This work investigates advanced heat transfer mechanisms in boundary-layer flow of nanofluids over a stretchable sheet. The comprehensive model integrates radiation effects, Brownian motion, thermophoresis, Cattaneo-Christov heat flux and Magnetohydrodynamics (MHD). Nanofluids, composed of a base fluid with suspended nanoparticles, exhibit distinct thermophysical properties crucial for influencing heat and mass transfer dynamics. Through rigorous numerical analysis, key parameters such as nanoparticle volume fraction, stretching sheet velocity, Cattaneo-Christov parameter, radiation parameter, and magnetic field strength are examined. The findings reveal intricate interactions among these parameters, providing a thorough understanding of their combined impact on temperature and velocity characteristics inside the boundary layer. This research contributes significantly to fundamental knowledge in nanofluid dynamics and provides practical insights for optimizing heat transfer processes and fluid behavior over-stretching surfaces, especially in the context of advanced heat transfer mechanisms. The implications extend across diverse engineering disciplines and materials science, offering valuable guidance for designing and improving processes involving nanofluid flows over-stretching sheets. With respect to the magnetic field parameter, the fluid velocity exhibits a decreasing attitude.

The temperature function enhances with higher $$\mathcal{R}$$
R
values but diminishes with increasing $$\mathcal{P}\mathcalligra{r}$$

P
r

values.
Discontinuation of brace treatment in adolescent idiopathic scoliosis (AIS): a scoping review
Authors: Swaby Lizzie , Cui Mengwei , Cole Ashley
Published: May 2024

Purpose

Brace treatment for adolescent idiopathic scoliosis (AIS) is usually prescribed for 20–40° curves in patients with growth potential. The aim is to reduce the risk of curve progression during growth and to avoid the curve reaching a surgical threshold. Having as small a curve as possible at skeletal maturity will reduce the risk of curve progression during adult life. While evidence exists for brace treatment in AIS, there is disagreement on how and when to discontinue bracing. The purpose of this review was to investigate what criteria have been reported for initiating brace cessation and published weaning protocols and to look at estimates of the number of patients that may progress > 5 degrees after the end of growth.

Methods

This scoping review summarizes existing knowledge on the best time to stop bracing in AIS patients, how to “wean,” and what happens to spinal curves after bracing. Searches were carried out through MEDLINE, EMBASE, and PsycINFO in April 2022. A total of 1936 articles were reduced to 43 by 3 reviewers. Full papers were obtained, and data were extracted.

Results

Weaning was most commonly determined by Risser 4 (girls) and 5 (boys). Other requirements included 2 years post-menarche and no growth in standing/sitting height for 6 months. Skeletal maturity assessed from hand and wrist radiographs, e.g., Sanders’ stage; distal radius and ulnar physes, could determine the optimal weaning time to minimize curve progression. Complete discontinuation was the most common option at skeletal maturity; variations on weaning protocols involved gradual reduction of bracing over 6–12 months. Curve progression after weaning is common. The 12 studies reporting early curve progression after brace weaning found a mean Cobb angle progression of 3.8° (n = 1655). From the seven studies reporting early curve progression by > 5 degrees, there were 236/700 (34%) patients. There is limited information on risk factors to predict early curve progression after finishing brace treatment with larger curves, especially those over 40 degrees possibly having more chance of progression.

Conclusion

Curve progression after bracing cessation is a negative outcome for patients who have tolerated bracing for several years, especially if surgery is required. The literature shows that when to start brace cessation and weaning protocols vary. Approximately 34% of patients progressed by more than 5 degrees at 2–4 years after brace cessation or weaning. Larger curves seem more likely to progress. More research is needed to evaluate the risk factors for curve progression after brace treatment, defining the best time to stop bracing based on the lowest risk of curve progression and whether there is any benefit to weaning.
Friction welding of UFG copper using the W2Mi prototype machine
Authors: Morawiński Łukasz , Jasiński Cezary , Goliński Jacek , Chmielewski Tomasz M.
Published: May 2024

When welding ultra-fine-grained metals using conventional methods, the microstructure in the joint area is degraded (mainly due to recrystallization) in the heat-affected zone and a significant deterioration of mechanical properties, including joint strength. The aim of the research presented in this article was to identify the possibility of obtaining joints with strength close to initial material using friction welding of metal materials with ultra-fine grain. For this purpose, UFG (ultra-fine-grained) material was produced from technically pure M1Ez4 copper using a hybrid SPD (severe plastic deformation) process. The welding process was carried out on a machine with a prototype design that allows minimizing the welding time, while generating high force. The process parameters used on the prototype machine resulted in an increase in the hardness of the material by 4% in the joint area. The strength of the joint compared to the base material decreased slightly by 2%. The tests carried out proved that, using appropriate process parameters, it is possible to obtain a UFG metal joint without a decrease in its mechanical strength.
Low expectations within conservative wing of discourse coalition for innovation and technoscience: integrating vanguard visions to therapeutic consent
Authors: Altinok Ozan Altan
Published: May 2024

Drawing on the sociology of expectations, this paper inquires what objects, promises, and audiences are invoked in two examples of biotechnology discourse on organoids, MCELS (Multicellular Engineered Living Systems) in the USA and REBIRTH (From REgenerative BIology to Reconstructive THerapy) in Germany, and how that affects therapeutic consent. Therapeutic consent discussion in the literature has been focusing on singular discourse on the objects of biotechnology. This paper focuses on making of organoids embedded in two very large research projects of biotechnology in two comparative cases to fill the gap between cultures of imaginations and discourses. The paper claims that (a) both projects are connected through shared objects within vanguard visions joined through a discourse coalition. The discourse coalitions that are making them further can be connected at the object level both by the low expectations and the techno-scientific imaginaries that are more relevant to public imagination by nested frameworks of vanguard visions and sociotechnical imaginaries. This connection is necessary for the object to be considered within the research and development of the object, whereas when the research programme is finished and the object itself is delivered, the low expectation and the calibration thereafter is dependent on this network (b) When the object [organoid] itself is a research object and a part of a discourse coalition is and an applied healthcare object at the same time, lowering of expectations and recalibration of the higher expectations are necessary for debates around consent as enabling conditions of consent in the very first place.
Techno-economics of multi-stage reverse electrodialysis for blue energy harvesting
Authors: Wang Lu , Zhao Yanan , Long Rui , Liu Zhichun , Liu Wei
Published: May 2024

Multi-stage reverse electrodialysis (MSRED) offers a promising way for efficient salinity gradient energy harvesting. Here, an improved model of the MSRED system under serial control strategy is proposed. The technical–economic analysis is conducted with considering discount, depreciation and different regional tax and electricity price levels under the maximum net power output conditions. Results reveal that net power output and energy efficiency both increase first with increasing stage numbers, reach their maximum values, and then decrease. For 5 M/0.05 M solutions, the optimal net power output of 4.98 kW is obtained at the stage number n = 12. The optimal stage number corresponding to the maximum net power increases with increasing feed solution concentrations. Due to the compromise between net power generation and capital cost, there exist optimal stage numbers leading to the lowest LCOE and largest NPV, respectively. Higher feed solution concentration can significantly decrease the system LCOE and increase the NPV. The optimal stage number corresponding to the maximum NPV increases with increasing feed solution concentrations. In Germany, for 5 M/0.05 M solutions, the lowest LCOE of 0.061 €·kWh−1 is achieved at n = 3 while the highest NPV over the system lifecycle of 52,005 € is obtained at n = 8. Lower tax, higher electricity price, appropriate membrane price and stage numbers, and high salinity gradient sources can significantly accelerate the commercial completeness of the MSRED systems.
“Fighting Pirates” as a Paradigm
Authors: Höhn Philipp
Published: May 2024

This article analyzes the emergence of the paradigm of “piracy” and “fighting pirates” among the urban elites of the Hanse city of Lübeck in the fifteenth and sixteenth centuries. While recent studies of maritime conflict management in this period have questioned the use of the term “piracy,” this study shows that towns such as Lübeck instrumentalized a discourse on “piracy” to criminalize and marginalize their competitors at a moment of structural economic change. A close reading of the records of the Lübeck Bergenfahrer, a guild of merchants trading to Norway, demonstrates how this concept was mobilized to justify actors’ own violence as a struggle against so-called pirates and thus to stabilize group identities. The notion of “fighting pirates” gradually became a paradigm for urban elites like the Bergenfahrer, representing their social coherence as communities of violence.
How Men of Letters Invented a Scientific Revolution: The Emergence of a Narrative in the Age of Louis XIV
Authors: Rabinovitch Oded
Published: May 2024

In contrast to other scientific renaissances, the culture forged in seventeenth-century Europe became an enduring phenomenon rather than dissipating within a few generations. In an effort to understand the persistence of European science, this article uses the case study of France under Louis XIV (r. 1643–1715) to argue that men of letters played a crucial role in the legitimation of the nascent scientific movement. These men of letters enjoyed a social, intellectual, and aesthetic affinity with the “new science” and developed a narrative of scientific change that foregrounded the idea of a radical break with the past. They diffused this narrative among the cultural elite, mobilizing recent thinkers, discoveries, and scientific instruments as they participated in wide-ranging debates, regardless of whether they supported modern innovations or classical models. In so doing, they invented the narrative of a “scientific revolution,” a construction that has wielded a profound influence over the social and cultural history of European science.
Otoendoscopy as a better preoperative predictor than pure tone audiometry for ossicular erosion in mucosal chronic otitis media
Authors: Bhardwaj Abhishek , Gupta Kartikesh , PS Suji , Malhotra Manu , Priya Madhu , Varshney Saurabh , Sood Rachit , Singh Arpana
Published: May 2024

Objective

To compare the diagnostic accuracy of angled otoendoscopy with pure tone audiometry in predicting ossicular discontinuity in patients of mucosal chronic otitis media.

Methods

Ninety-four patients were included in this prospective study. A 2.7-mm 30° otoendoscope was used to examine ossicular status preoperatively. Hearing thresholds were recorded by pure tone audiometry. Intraoperative ossicular status was recorded as the gold standard. Otoendoscopic findings were recorded as per the criteria has been devised by the authors of this manuscript.

Results

Otoendoscopy was conclusive in 56 (59.6 per cent) patients, with 100 per cent sensitivity, 95.56 per cent specificity, 84.62 per cent positive predictive value, and 100 per cent negative predictive value in the conclusive group. Overall (in 94 patients), diagnostic test values of otoendoscopy were 73.33 per cent sensitivity, 97.47 per cent specificity, 84.62 per cent positive predictive value, and 95.06 per cent negative predictive value. As per the ROC curve, air–bone gap > 38.12dB had the optimal diagnostic test values, with 73 per cent sensitivity, 72 per cent specificity, 33.3 per cent positive predictive value, and 93.4 per cent negative predictive value.

Conclusion

Angled otoendoscopy has better diagnostic accuracy (93.6 per cent) than pure tone audiometry (72.3 per cent; p < 0.001) for preoperative ossicular discontinuity prediction in patients of mucosal chronic otitis media.
Neutrophils and neutrophil extracellular traps in oral health and disease
Authors: Kim Tae Sung , Moutsopoulos Niki M.
Published: May 2024

Neutrophils perform essential functions in antimicrobial defense and tissue maintenance at mucosal barriers. However, a dysregulated neutrophil response and, in particular, the excessive release of neutrophil extracellular traps (NETs) are implicated in the pathology of various diseases. In this review, we provide an overview of the basic concepts related to neutrophil functions, including NET formation, and discuss the mechanisms associated with NET activation and function in the context of the prevalent oral disease periodontitis.
Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer
Authors: Park Wonyoung , Wei Shibo , Xie Chu-Long , Han Jung Ho , Kim Bo-Sung , Kim Bosung , Jin Jung-Sook , Yang Eun-Sun , Cho Min Kyoung , Ryu Dongryeol , Yang Hao-Xian , Bae Sung-Jin , Ha Ki-Tae
Published: May 2024

Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.
Adult attitudes to sustainable dentistry in Trinidad and Tobago and their willingness to accept alternatives
Authors: Hoyte Trudee , James Akini , Carr Deysha , Teelucksingh Abbinah Donatien Andrew , Mossey Peter
Published: May 2024

Introduction

Attitudes towards and willingness to accept alternatives for sustainable dentistry in Trinidad and Tobago have never been assessed. Market research aids in the understanding of the behaviours of people. Since change can be enacted by public pressure, it is worth engaging the public through research to understand their attitudes and which changes they are willing to accept.

Method

A self-administered questionnaire was distributed to private and public dental clinics. The questionnaire assessed attitude towards and willingness to accept alternatives which decrease the effect of dental treatment on the environment.

Results

The study consisted of 1267 participants. Participants were mostly female, older, employed and mainly of African descent. Participants reported a very positive attitude towards sustainable dentistry (Mean = 3.89, SD = 0.8). and were moderately willing to accept alternatives such as a longer appointment time (Mean 3.47, SD = 0.73) and pay more for their dental treatments (Mean=3.00, SD = 0.87). There was a strong positive correlation with attitudes to sustainable dentistry and participants willingness to accept alternatives such as a longer appointment time (r = 0.658, p < 0.05).

Conclusion

The adult population had an overall positive attitude towards sustainable dentistry and was willing to accept alternatives so that their dental treatment would have less impact on the environment.
Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology
Authors: Jackson Joshua , Hoffmann Christian , Scifo Enzo , Wang Han , Wischhof Lena , Piazzesi Antonia , Mondal Mrityunjoy , Shields Hanna , Zhou Xuesi , Mondin Magali , Ryan Eanna B. , Döring Hermann , Prehn Jochen H. M. , Rottner Klemens , Giannone Gregory , Nicotera Pierluigi , Ehninger Dan , Milovanovic Dragomir , Bano Daniele
Published: May 2024

Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence thatwsp-1/WASL loss of functionalters the number and dynamics of α-Syn inclusions in the nematodeCaenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.
Impact of the thyroid hormone T3 and its nuclear receptor TRα1 on colon cancer stem cell phenotypes and response to chemotherapies
Authors: Giolito Maria Virginia , Bodoirat Serguei , La Rosa Theo , Reslinger Mathieu , Guardia Gabriela D. A. , Mourtada Jana , Claret Leo , Joung Alain , Galante Pedro A. F. , Penalva Luiz O. F. , Plateroti Michelina
Published: May 2024

Colorectal cancers (CRCs) are highly heterogeneous and show a hierarchical organization, with cancer stem cells (CSCs) responsible for tumor development, maintenance, and drug resistance. Our previous studies showed the importance of thyroid hormone-dependent signaling on intestinal tumor development and progression through action on stem cells. These results have a translational value, given that the thyroid hormone nuclear receptor TRα1 is upregulated in human CRCs, including in the molecular subtypes associated with CSC features. We used an established spheroid model generated from the human colon adenocarcinoma cell line Caco2 to study the effects of T3 and TRα1 on spheroid formation, growth, and response to conventional chemotherapies. Our results show that T3 treatment and/or increased TRα1 expression in spheroids impaired the response to FOLFIRI and conferred a survival advantage. This was achieved by stimulating drug detoxification pathways and increasing ALDH1A1-expressing cells, including CSCs, within spheroids. These results suggest that clinical evaluation of the thyroid axis and assessing TRα1 levels in CRCs could help to select optimal therapeutic regimens for patients with CRC.
Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids
Authors: Song Myeongjin , Choi Da Bin , Im Jeong Suk , Song Ye Na , Kim Ji Hyun , Lee Hanbyeol , An Jieun , Kim Ami , Choi Hwan , Kim Joon-Chul , Han Choongseong , Jeon Young Keul , Kim Sung Joon , Woo Dong-Hun
Published: May 2024

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.
TM7SF2-induced lipid reprogramming promotes cell proliferation and migration via CPT1A/Wnt/β-Catenin axis in cervical cancer cells
Authors: Liu Hejing , Liu Yi , Zhou Yujia , Chen Xin , Pan Shuya , Zhou Qingfeng , Ji Huihui , Zhu Xueqiong
Published: May 2024

Cervical cancer poses a serious threat to women’s health globally. Our previous studies found that upregulation of TM7SF2, which works as an enzyme involved in the process of cholesterol biosynthesis expression, was highly correlated with cervical cancer. However, the mechanistic basis of TM7SF2 promoting cervical cancer progression via lipid metabolism remains poorly understood. Therefore, quantification of fatty acids and lipid droplets were performed in vitro and in vivo. The protein-protein interaction was verified by Co-IP technique. The mechanism and underlying signaling pathway of TM7SF2 via CPT1A associated lipid metabolism in cervical cancer development were explored using Western blotting, IHC, colony formation, transwell assay, and wound healing assay. This study reported that overexpression of TM7SF2 increased fatty acids content and lipid droplets both in vivo and in vitro experiments. While knockout of TM7SF2 obviously attenuated this process. Moreover, TM7SF2 directly bonded with CPT1A, a key enzyme in fatty acid oxidation, and regulated CPT1A protein expression in cervical cancer cells. Notably, the proliferation and metastasis of cervical cancer cells were elevated when their CPT1A expression was upregulated. Then, rescue assay identified that CPT1A overexpressed could enhance the cell viability and migration in TM7SF2-knockout cells. Furthermore, depletion of TM7SF2 significantly inhibited WNT and β-catenin proteins expression, which was enhanced by CPT1A-overexpressed. The proliferation and migration of cervical cancer cells were reversed in CPT1A-overexpressed cells with the treatment of MSAB, an inhibitor of Wnt/β-Catenin pathway. This study put forward an idea that TM7SF2-induced lipid reprogramming promotes proliferation and migration via CPT1A/Wnt/β-Catenin axis in cervical cancer, underlying the progression of cervical cancer.
LARP4B promotes hepatocellular carcinoma progression and impairs sorafenib efficacy by activating SPINK1-mediated EGFR pathway
Authors: Wang Chuanxu , Dong Rui , Yang Feicheng , Zheng Lu , Liu Yingling , Yan Yue , Zhang Mengjie , Ni Bing , Li Jing
Published: May 2024

La-related proteins (LARPs) regulate gene expression by binding to RNAs and exhibit critical effects on disease progression, including tumors. However, the role of LARP4B and its underlying mechanisms in the progression of hepatocellular carcinoma (HCC) remain largely unclear. In this study, we found that LARP4B expression is upregulated and correlates with poor prognosis in patients with HCC. Gain- and loss-of-function assays showed that LARP4B promotes stemness, proliferation, metastasis, and angiogenesis in vitro and in vivo. Furthermore, LARP4B inhibition enhances the antitumor effects of sorafenib and blocks the metastasis-enhancing effects of low sorafenib concentrations in HCC. Mechanistically, LARP4B expression is upregulated by METTL3-mediated N6-methyladenosine (m6A)-IGF2BP3-dependent modification in HCC. RNA- and RNA immunoprecipitation (RIP)- sequencing uncovered that LARP4B upregulates SPINK1 by binding to SPINK1 mRNA via the La motif and maintaining mRNA stability. LARP4B activates the SPINK1-mediated EGFR signaling pathway, which supports stemness, progression and sorafenib resistance in HCC. Additionally, a positive feedback loop with the LARP4B/SPINK1/p-AKT/C/EBP-β axis is responsible for the sorafenib-therapeutic benefit of LARP4B depletion. Overall, this study demonstrated that LARP4B facilitates HCC progression, and LARP4B inhibition provides benefits to sorafenib treatment in HCC, suggesting that LARP4B might be a potential therapeutic target for HCC.
Training an Ising machine with equilibrium propagation
Authors: Laydevant Jérémie , Marković Danijela , Grollier Julie
Published: May 2024

Ising machines, which are hardware implementations of the Ising model of coupled spins, have been influential in the development of unsupervised learning algorithms at the origins of Artificial Intelligence (AI). However, their application to AI has been limited due to the complexities in matching supervised training methods with Ising machine physics, even though these methods are essential for achieving high accuracy. In this study, we demonstrate an efficient approach to train Ising machines in a supervised way through the Equilibrium Propagation algorithm, achieving comparable results to software-based implementations. We employ the quantum annealing procedure of the D-Wave Ising machine to train a fully-connected neural network on the MNIST dataset. Furthermore, we demonstrate that the machine’s connectivity supports convolution operations, enabling the training of a compact convolutional network with minimal spins per neuron. Our findings establish Ising machines as a promising trainable hardware platform for AI, with the potential to enhance machine learning applications.
Charge density waves tuned by biaxial tensile stress
Authors: Gallo–Frantz A. , Jacques V. L. R. , Sinchenko A. A. , Ghoneim D. , Ortega L. , Godard P. , Renault P.-O. , Hadj-Azzem A. , Lorenzo J. E. , Monceau P. , Thiaudière D. , Grigoriev P. D. , Bellec E. , Le Bolloc’h D.
Published: May 2024

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature Tc displays a linear dependence with $$\left\vert a/c-1\right\vert$$

a
/
c
−
1

while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and Tc in RTe3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter.
Unraveling the mechanisms of PAMless DNA interrogation by SpRY-Cas9
Authors: Hibshman Grace N. , Bravo Jack P. K. , Hooper Matthew M. , Dangerfield Tyler L. , Zhang Hongshan , Finkelstein Ilya J. , Johnson Kenneth A. , Taylor David W.
Published: May 2024

CRISPR-Cas9 is a powerful tool for genome editing, but the strict requirement for an NGG protospacer-adjacent motif (PAM) sequence immediately next to the DNA target limits the number of editable genes. Recently developed Cas9 variants have been engineered with relaxed PAM requirements, including SpG-Cas9 (SpG) and the nearly PAM-less SpRY-Cas9 (SpRY). However, the molecular mechanisms of how SpRY recognizes all potential PAM sequences remains unclear. Here, we combine structural and biochemical approaches to determine how SpRY interrogates DNA and recognizes target sites. Divergent PAM sequences can be accommodated through conformational flexibility within the PAM-interacting region, which facilitates tight binding to off-target DNA sequences. Nuclease activation occurs ~1000-fold slower than for Streptococcus pyogenes Cas9, enabling us to directly visualize multiple on-pathway intermediate states. Experiments with SpG position it as an intermediate enzyme between Cas9 and SpRY. Our findings shed light on the molecular mechanisms of PAMless genome editing.