bluuebunny/crossref_metadata_2025 huggingface dataset:
TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities
Authors: Möller Katharina , Gulzar Tayyaba , Lennartz Maximilian , Viehweger Florian , Kluth Martina , Hube-Magg Claudia , Bernreuther Christian , Bawahab Ahmed Abdulwahab , Simon Ronald , Clauditz Till S. , Sauter Guido , Schlichter Ria , Hinsch Andrea , Kind Simon , Jacobsen Frank , Burandt Eike , Frost Nikolaj , Reck Martin , Marx Andreas H. , Krech Till , Lebok Patrick , Fraune Christoph , Steurer Stefan
Published: October 2024

Thyroid transcription factor 1 (TTF-1) immunohistochemistry (IHC) is routinely used for the distinction of primary pulmonary adenocarcinomas. However, TTF-1 can also occur in other malignancies. A tissue microarray containing 17,772 samples from 152 different tumor types was analyzed. Napsin-A, CK20, SATB2, FABP1, and Villin-1 IHC data were available from previous studies. TTF-1 staining was seen in 82 of 152 tumor categories including thyroidal cancers (19–100%), adenocarcinomas (94%), neuroendocrine tumors (67%) of the lung, small cell neuroendocrine carcinomas (71–80%), mesenchymal tumors (up to 42%), and thymomas (39%). Comparative analysis of TTF-1 and Napsin-A revealed a sensitivity/specificity of 94%/86% (TTF-1), 87%/98% (Napsin-A), and 85%/99.1% (TTF-1 and Napsin-A) for the distinction of pulmonary adenocarcinomas. Combined analysis of TTF-1 and enteric markers revealed a positivity for TTF-1 and at least one enteric marker in 22% of pulmonary adenocarcinomas but also a TTF-1 positivity in 6% of colorectal, 2% of pancreatic, and 3% of gastric adenocarcinomas. TTF-1 is a marker of high sensitivity but insufficient specificity for pulmonary adenocarcinomas. A small fraction of TTF-1-positive gastrointestinal adenocarcinomas represents a pitfall mimicking enteric-type pulmonary adenocarcinoma. Combined analysis of TTF-1 and Napsin-A improves the specificity of pulmonary adenocarcinoma diagnosis.
Extracorporeal pediatric renal replacement therapy: diversifying application beyond kidney failure
Authors: Chanchlani Rahul , Askenazi David , Bayrakci Benan , Deep Akash , Morgan Jolyn , Neumayr Tara M.
Published: October 2024

The utilization of extracorporeal renal replacement therapy (RRT), including continuous renal replacement therapy (CRRT) and hemodialysis (HD), beyond the treatment of volume overload and acute kidney injury (AKI) has witnessed a significant shift, demonstrating the potential to improve patient outcomes for a range of diseases. This comprehensive review explores the non-kidney applications for RRT platforms in critically ill children, focusing on diverse clinical scenarios such as sepsis, inborn errors of metabolism, liver failure, drug overdose, tumor lysis syndrome, and rhabdomyolysis. In the context of sepsis and septic shock, RRT not only facilitates fluid, electrolyte, and acid/base homeostasis, but may offer benefits in cytokine regulation, endotoxin clearance, and immunomodulation which may improve multi-organ dysfunction as well as hemodynamic challenges posed by this life-threatening condition. RRT modalities also have an important role in caring for children with inborn errors of metabolism, liver failure, and tumor lysis syndrome as they can control metabolic derangements with the efficient clearance of endogenous toxins in affected children. In cases of drug overdose, RRT is a crucial tool for rapid extracorporeal clearance of exogenous toxins, mitigating potential organ damage. The intricate interplay between liver failure and kidney function is examined, elucidating the role of RRT and plasma exchange in maintaining fluid and electrolyte balance when hepatic dysfunction complicates the clinical picture. Furthermore, RRT and HD are explored in the context of rhabdomyolysis, highlighting their utility in addressing AKI secondary to traumatic events and crush syndrome.

Graphical abstract
Early taxane exposure and neurotoxicity in breast cancer patients
Authors: Cimbro Erika , Dessì Mariele , Ziranu Pina , Madeddu Clelia , Atzori Francesco , Lai Eleonora , Pretta Andrea , Mariani Stefano , Donisi Clelia , Spanu Dario , Pozzari Marta , Murgia Sara , Saba Giorgio , Codipietro Claudia , Palmas Enrico , Sanna Giorgia , Semonella Francesca , Sardo Salvatore , Finco Gabriele , Scartozzi Mario
Published: October 2024

Introduction

Breast cancer is the most diagnosed tumor and a leading cause of cancer death in women worldwide. Taxanes are the most used chemotherapeutic agents and are strictly connected to neurotoxicity. Taxane-induced neuropathy (TIN) significantly impacts patients’ quality of life (QOL). Early identification and management of TIN could improve preventive strategies to preserve patients’ QOL during and after breast cancer treatment.

Objective

This prospective, observational study aimed to evaluate the taxane-induced neuropathy (TIN) in early breast cancer patients treated with weekly paclitaxel at an earlier stage and identify any correlation between TIN and QOL.

Methods

Data from stage I-III breast cancer patients treated with taxane-based therapy between 2018 and 2022 were collected at the Medical Oncology Unit of the University Hospital of Cagliari. Peripheral neuropathy was evaluated using the NCI-CTCAE scale (National Cancer Institute, Common Terminology Criteria for Adverse Events) at every drug administration. In contrast, QOL was assessed using EORTC QLC-CIPN20 and FACT-Taxane questionnaire at baseline (T0), after 4 weeks (T1) and 12 (T2) weeks of treatment. Statistical analysis was performed to evaluate the correlation between neurotoxicity and QOL.

Results

Neurotoxicity incidence peaked at the third, fourth, and sixth week of treatment, with patients reporting grade 1 and 2 neurotoxicity. Simultaneously with increasing doses of paclitaxel, significant differences in QOL were observed in early treatment cycles relating to TIN presentation. Patients with higher neurotoxicity grades reported lower QOL scores.

Conclusions

Despite the absence of effective treatments to prevent paclitaxel-induced neurotoxicity, symptoms are managed through dosage reduction, delay, or treatment interruption. Future research should focus on identifying neuroprotective measures to avoid an irreversible decline in the quality of life for breast cancer survivors.
Preservation of emotional context in tweet embeddings on social networking sites
Authors: Maruyama Osamu , Yoshinaga Asato , Sawai Ken-ichi
Published: October 2024

In communication, emotional information is crucial, yet its preservation in tweet embeddings remains a challenge. This study aims to address this gap by exploring three distinct methods for generating embedding vectors of tweets: word2vec models, pre-trained BERT models, and fine-tuned BERT models. We conducted an analysis to assess the degree to which emotional information is conserved in the resulting embedding vectors. Our findings indicate that the fine-tuned BERT model exhibits a higher level of preservation of emotional information compared to other methods. These results underscore the importance of utilizing advanced natural language processing techniques for preserving emotional context in text data, with potential implications for enhancing sentiment analysis and understanding human communication in social media contexts.
A Reformulation of the Laminar Kinetic Energy Model to Enable Multi-mode Transition Predictions
Authors: Pacciani Roberto , Fang Yuan , Metti Leonardo , Marconcini Michele , Sandberg Richard
Published: October 2024

The paper describes the development of a novel transition/turbulence model based on the laminar kinetic energy concept. The model is intended as a base framework for data-driven improvements. Starting from a previously developed framework, mainly aimed at separated-flow transition predictions, suitable terms for model generalization are identified and reformulated for handling different transition modes, namely bypass and separated-flow modes. The ideology for the definition of new terms has its roots in mixing phenomenological and correlation-based arguments, ensuring generality and flexibility and allowing a variety of lines of action for improving model components via machine-learning approaches. The model calibration, carried out with reference to flat plate test cases subjected to different pressure gradients and freestream turbulence levels, is discussed in detail. Although the constructed model is calibrated on a group of classic flat plat cases, the validation campaign, mostly carried out on gas turbine cascades, demonstrates its ability to predict transitional flows with engineering accuracy. Finally, while the model is not specifically developed for natural transition predictions, satisfactory predictions are obtained in scenarios with low freestream turbulence for flat plate and airfoil flows.
Capture, commodify, kill: Legitimized harms and industrial meatpacking in the united states
Authors: León Kenneth Sebastian , Ken Ivy , Martin Theo
Published: October 2024

Slaughtering and processing animals on an industrial scale are complicated activities that are both highly prominent in the food system and intentionally concealed from the public. The structural violence enacted within this industry deserves attention as a direct form of state-corporate harm. To this end, this paper invokes Tombs and Whyte’s imaginaries of corporate crime to understand what they might call the “ceaseless repetition” through which harms against workers, animals, and the environment in the meatpacking industry are enacted. From this application in the context of a Marxian analysis of primitive accumulation, we have determined the importance of capital’s ability to capture, commodify, and kill (CCK) – concepts we offer together as a heuristic device to highlight the types of harm done to labor, animals, and land, and to explain how these harms are accomplished. Drawing on the copious literature on meatpacking, as well as our own direct observations of the industry, this paper emphasizes the role of food systems for white-collar and corporate crime specialists interested in policy and social change.
Multilateral environmental agreements as information media: their functions and a theoretical framework
Authors: Ohtani Shimon
Published: October 2024

Multilateral Environmental Agreements (MEAs), which have increased since the 1970s to address global environmental issues, have persistently tended to be analyzed and evaluated in terms of their aspects as international law in global environmental governance studies. However, research to improve the quality of communication by identifying information that influences the inner lives of non-state actors, especially their normative attitudes and behavioral intentions that directly affect their behavioral change, still needs to be established. We focus on another aspect, MEAs as information media. In the process of gradual development from their entry into force, MEAs continuously absorb all kinds of information and release new information. We named such an information refinement process “The Metabolism of Information.” Emphasizing the function of MEAs as information media promotes a shift to emerging research approaches emphasizing the information transfer process. Among these, we propose one theoretical framework, focusing on the utility of Sentiment Analysis using Natural Language Processing (NLP) and the need to combine it with Environmental Psychological theories to apply the results. This integrated framework has modeled a series of processes that make the most of the immediacy of information technology and enable policy reflection with immediate effect and is expected to be discussed as bridging the gap between Sentiment Analysis and practical policy building. In the future, investing in human resources and technical equipment and interdisciplinary collaboration would be crucial to address ethical issues in anticipation of an accelerated shift to data-driven research approaches to promote MEAs as information media.
Automatic Enrollment in Patient Portal Systems Mitigates the Digital Divide in Healthcare: An Interrupted Time Series Analysis of an Autoenrollment Workflow Intervention
Authors: Milanfar Leila , Soulsby William Daniel , Ling Nicole , O’Brien Julie S. , Oates Aris , McCulloch Charles E.
Published: October 2024

Purpose

Racial and ethnic healthcare disparities require innovative solutions. Patient portals enable online access to health records and clinician communication and are associated with improved health outcomes. Nevertheless, a digital divide in access to such portals persist, especially among people of minoritized race and non-English-speakers. This study assesses the impact of automatic enrollment (autoenrollment) on patient portal activation rates among adult patients at the University of California, San Francisco (UCSF), with a focus on disparities by race, ethnicity, and primary language.

Materials and methods

Starting March 2020, autoenrollment offers for patient portals were sent to UCSF adult patients aged 18 or older via text message. Analysis considered patient portal activation before and after the intervention, examining variations by race, ethnicity, and primary language. Descriptive statistics and an interrupted time series analysis were used to assess the intervention’s impact.

Results

Autoenrollment increased patient portal activation rates among all adult patients and patients of minoritized races saw greater increases in activation rates than White patients. While initially not statistically significant, by the end of the surveillance period, we observed statistically significant increases in activation rates in Latinx (3.5-fold, p = < 0.001), Black (3.2-fold, p = 0.003), and Asian (3.1-fold, p = 0.002) patient populations when compared with White patients. Increased activation rates over time in patients with a preferred language other than English (13-fold) were also statistically significant (p = < 0.001) when compared with the increase in English preferred language patients.

Conclusion

An organization-based workflow intervention that provided autoenrollment in patient portals via text message was associated with statistically significant mitigation of racial, ethnic, and language-based disparities in patient portal activation rates. Although promising, the autoenrollment intervention did not eliminate disparities in portal enrollment. More work must be done to close the digital divide in access to healthcare technology.
Varieties of Consequentialism and Deontology in Theories of Tort Law
Authors: Slavny Adam
Published: October 2024

An important contribution of Gregory Keating’s Reasonableness and Risk is to mount objections to law and economics whilst articulating an alternative deontological vision of tort law to that offered by corrective justice theorists. In this paper I offer two reservations about Keating’s account. One is that some forms of consequentialism can accommodate at least some aspects of his deontological theory, so we must be careful to distinguish between claims that strike at the heart of consequentialism and those that are only a problem for wealth maximisation. The second is that there are yet other varieties of deontology besides Kantianism and Keating’s alternative to it, and while I accept some of Keating’s claims, I think we should reject others. I will make the case for each of these reservations via discussion of three core features of Keating’s account: the harm/benefit asymmetry, the commitment to objective rather than subjective valuation, and his justification of strict liability.
Implementation of an exact completing method of generation for face-milled spiral bevel gears with uniform depth taper
Authors: Gonzalez-Perez Ignacio , Fuentes-Aznar Alfonso
Published: October 2024

This paper proposes an exact completing method of generation of face-milled spiral bevel gears with uniform depth taper. This method ensures localized bearing contact without kinematic transmission errors in both directions of rotation. Both sides of the tooth are generated simultaneously using the same set of basic machine tool settings. A tip relief on the tooth surfaces is the only required microgeometry modification to achieve a smooth transition of load between consecutive pairs of teeth. An analytical approach to determine the basic machine tool settings and select the grinding cutter parameters has been also developed. The selection of the nominal cutter radius follows the recommendations of Information Sheet AGMA 22849-A12. The basis for alignment error compensation has been also established. Tooth contact and stress analyses demonstrate the advantages and limitations of the proposed method, making it suitable for applications with higher power demands for the drive side than for the coast side.
Reliability of Theory of Mind Tasks in Schizophrenia, ASD, and Nonclinical Populations: A Systematic Review and Reliability Generalization Meta-analysis
Authors: Tsui Harry Kam Hung , Wong Ting Yat , Ma Chak Fai , Wong Ting Eva , Hsiao Janet , Chan Sherry Kit Wa
Published: October 2024

Though theory of mind (ToM) is an important area of study for different disciplines, however, the psychometric evaluations of ToM tasks have yielded inconsistent results across studies and populations, raising the concerns about the accuracy, consistency, and generalizability of these tasks. This systematic review and meta-analysis examined the psychometric reliability of 27 distinct ToM tasks across 90 studies involving 2771 schizophrenia (SZ), 690 autism spectrum disorder (ASD), and 15,599 nonclinical populations (NC). Findings revealed that while all ToM tasks exhibited satisfactory internal consistency in ASD and SZ, about half of them were not satisfactory in NC, including the commonly used Reading the Mind in the Eye Test and Hinting Task. Other than that, Reading the Mind in the Eye Test showed acceptable reliability across populations, whereas Hinting Task had poor test–retest reliability. Notably, only Faux Pas Test and Movie for the Assessment of Social Cognition had satisfactory reliability across populations albeit limited numbers of studies. However, only ten studies examined the psychometric properties of ToM tasks in ASD adults, warranting additional evaluations. The study offered practical implications for selecting ToM tasks in research and clinical settings, and underscored the importance of having a robust psychometric reliability in ToM tasks across populations.
Identifying and classifying broader scale of disaster impacts to better inform disaster management policies and practice
Authors: Tennakoon Kishani Priyangi , Serrao-Neumann Silvia , Cretney Raven
Published: October 2024

Disasters are often assessed by factors such as their magnitude, severity and impact on affected communities. Typically, disaster management policies are largely informed by learnings from large-scale disasters. Many studies, however, have shown that cumulative smaller scale disaster impacts have similar outcomes comparable to larger scale disasters. This indirectly contributes to a lack of consistency in and paucity of data related to both smaller-scale disasters and their associated cumulative impacts. This paper argues that greater attention needs to be paid to collecting disaster impact data on a range of disaster-scale events along with their cumulative impacts to better inform disaster management policies and practice. The paper aims to test the hypothesis that a better understanding of a wide range of disaster scale types and their impacts on communities, including small-scale disasters, enables the development of more just, consistent and equitable disaster management policies and practice. Analysing economic costs, evacuation and rainfall data from past flood events that affected Aotearoa-New Zealand over the last three decades, the paper found discrepancies and lack of coherence in disaster data collection and reporting, along with a predominant reliance on rainfall intensity data for disaster risk reduction and planning. The findings also confirmed the importance of identifying economic damages for a range of disaster scales, including those from small-scale disasters. This highlights the need for developing a spectrum to better classify and identify disaster impacts based on various spatial and temporal contexts. The paper concludes by affirming that such database would provide much needed evidence for developing a methodology that enables the identification of the level of disaster impacts; thereby guiding the implementation of more just, consistent and equitable disaster management policies and practice.
In search of lost principles: generic generalism in aesthetics and ethics
Authors: Lord Errol
Published: October 2024

I defend a form of generalism in ethics and aesthetics. Generalism about a domain D is the view that there are principles that play an explanatory role in the metaphysics of D and can be used in reasoning when thinking about D. I argue that in both aesthetics and ethics, there are generic generalizations that are principles. I do this by (i) explaining the nature of a particularly important kind of generic, (ii) argue that generics of this kind play a explanatory role, and (iii) argue that we licitly use these truths in reasoning about ethics and aesthetics.
Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25–57% elevation in risk
Authors: Ungvari Zoltan , Fekete Mónika , Varga Peter , Lehoczki Andrea , Fekete János Tibor , Ungvari Anna , Győrffy Balázs
Published: October 2024

The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case–control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24–1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38–1.78, p = 0.01) for males and 1.25 (95% CI = 1.14–1.38, p < 0.01) for females. Case–control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98–1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case–control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case–control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.
Efficacy and Safety of Andexanet Alfa Versus Four Factor Prothrombin Complex Concentrate for Emergent Reversal of Factor Xa Inhibitor Associated Intracranial Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Sarhan Khalid , Mohamed Rashad G. , Elmahdi Reem Reda , Mohsen Youstina , Elsayed Asmaa , Zayed Dania Mosaad , Elkholi Menna A. , Gabr Nagat , El-Bialy Enjy M. , Serag Ibrahim
Published: October 2024

Factor Xa inhibitors (FXaI) are increasingly used for anticoagulation therapy, yet their association with intracranial hemorrhage poses a significant challenge. Although andexanet alfa (AA) and four-factor prothrombin complex concentrate (4F-PCC) have shown promise in reversing FXaI effects, their comparative efficacy and safety remain uncertain. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until May 16, 2024. Our primary outcomes were successful anticoagulation reversal, overall mortality (including 30-day and in-hospital mortality), and thromboembolic events. Secondary outcomes were length of hospital and intensive care unit stay and hematoma volume expansion. Data were pooled using a random-effects model. We included 16 eligible studies with a total of 2,977 patients. A statistically significant improvement in hemostatic efficacy rates was in favor of the AA group (risk ratio [RR] 1.10, 95% confidence interval [CI] 1.01–1.20, P = 0.02). Lower overall mortality rates were found in the AA group (RR 0.67, 95% CI 0.51–0.88, P = 0.004). However, no difference was found in 30-day mortality rates (RR 0.82, 95% CI 0.58–1.16, P = 0.26). In terms of thromboembolic events, more events were found in the AA group (RR 1.47, 95% CI 1.01–2.15, P = 0.046). AA was associated with a longer duration of hospital stay compared to 4F-PCC (mean difference [MD] 0.64, 95% CI 0.07–1.22, P = 0.03). Neither a significant difference in length of intensive care unit stay (MD 0.25, 95% CI − 0.36 to 0.86, P = 0.41) nor a significant difference in hematoma volume expansion was reported (MD − 0.89, 95% CI − 3.11 to 1.34, P = 0.435). Our results suggest that AA is superior to 4F-PCC in enhancing the hemostatic efficacy and reducing the overall and in-hospital mortality rates. More thromboembolic events are thought to be associated with the use of AA. However, more studies are required to validate whether the better results of AA in improving hemostatic efficacy are enough to make up for their higher cost and their possible risk of thromboembolic events.
Capivasertib and fulvestrant for patients with HR-positive/HER2-negative advanced breast cancer: analysis of the subgroup of patients from Japan in the phase 3 CAPItello-291 trial
Authors: Tokunaga Eriko , Iwata Hiroji , Itoh Mitsuya , Taira Tetsuhiko , Toyama Tatsuya , Mizuno Toshiro , Osaki Akihiko , Yanagita Yasuhiro , Nakamura Seigo , Nakamura Rikiya , Sambe Tomoko , Ozaki Toshiaki , Schiavon Gaia , Howell Sacha J. , Toi Masakazu
Published: October 2024

Background

In CAPItello-291, capivasertib–fulvestrant significantly improved progression-free survival (PFS) versus placebo–fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib–fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan.

Methods

Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint.

Results

Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib–fulvestrant and 41 to placebo–fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib–fulvestrant arm (hazard ratio 0.73; 95% CI 0.40–1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN–altered tumors, PFS favored the capivasertib–fulvestrant arm (hazard ratio 0.65; 95% CI 0.29–1.39), consistent with the global population. The adverse event profile of capivasertib–fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified.

Conclusion

Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib–fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.
Clinical translation and landscape of silver nanoparticles
Authors: Dias Manuel , Zhang Rui , Lammers Twan , Pallares Roger M.
Published: October 2024

Despite being clinically used for over a century, the benefits of silver nanoparticles are perennially under debate and dispute. In the last two decades, a revived interest in their therapeutic applications has resulted in a few new formulations transitioning into clinical trials. These metal nanomedicines are used in concrete applications that are defined by the physicochemical and biological features of the silver nanoconstructs, as well as their biodistribution profiles. Examples of these applications are topical antibacterial and antiviral therapies and wound healing, as these avoid concerns regarding the long-term accumulation of the nanomedicines in fenestrated organs after intravenous administration. Here, we discuss the current landscape of silver nanoparticles, and critically analyze the characteristics that endowed their transition and use in clinical settings.
Initial monitoring of a six-story lightweight timber frame building under different environmental conditions
Authors: Amaddeo Carmen , Dorn Michael , Martinelli Luca
Published: October 2024

This study presents a comprehensive investigation of the dynamic behavior of a six-story lightweight timber frame building through periodic and continuous ambient vibration tests. Seasonal changes in temperature and relative humidity can influence the dynamic response of timber buildings, by affecting stiffness, strength, and connection properties due to changes in moisture content. Systematic tests were performed from October 2022 until May 2024 to identify natural frequencies, damping ratios, and mode shapes of the building using five battery-driven data acquisition units equipped with 15 uni-axial accelerometers. Two different only-output frequency and time domain Operational Modal Analysis (OMA) methods were used to evaluate the dynamic properties of the building. Additionally, the building has been continuously monitored with temperature and humidity sensors since its construction. Results obtained from the periodic measurements highlighted the need for a permanent system to capture the transient changes in the modal parameters. A complementary permanent system to record the accelerations at the roof level was installed in May 2024. The modal parameters from in situ measurements were compared with those obtained from the Finite Element (FE) model of the structure. The FE model, calibrated through a multi-stage approach, incorporating non-structural elements, and varying imposed loads, showed good agreement with experimental data. Comparative analysis of the results obtained under different temperature and humidity conditions showed the effect of the environmental conditions on the building dynamics properties, for both periodic and permanent measurements. This study highlights the importance of continuous monitoring and detailed FE modeling in understanding the dynamic properties and long-term structural behavior under varying conditions. This information can be used to ensure that the building meets safety and performance requirements and to identify potential issues that may need to be addressed during the design and maintenance phases.
Fractional Wiener chaos: Part 1
Authors: Boguslavskaya Elena , Shishkina Elina
Published: October 2024

In this paper, we introduce a fractional analogue of the Wiener polynomial chaos expansion. It is important to highlight that the fractional order relates to the order of chaos decomposition elements, and not to the process itself, which remains the standard Wiener process. The central instrument in our fractional analogue of the Wiener chaos expansion is the function denoted as $${\mathcal {H}}_\alpha (x,y)$$

H
α

(
x
,
y
)

, referred to herein as a power-normalised parabolic cylinder function. Through careful analysis of several fundamental deterministic and stochastic properties, we affirm that this function essentially serves as a fractional extension of the Hermite polynomial. In particular, the power-normalised parabolic cylinder function with the Wiener process and time as its arguments, $${\mathcal {H}}_\alpha (W_t,t)$$

H
α

(

W
t

,
t
)

, demonstrates martingale properties and can be interpreted as a fractional Itô integral with 1 as the integrand, thereby drawing parallels with its non-fractional counterpart. To build a fractional analogue of polynomial Wiener chaos on the real line, we introduce a new function, which we call the extended Hermite function, by smoothly joining two power-normalized parabolic cylinder functions at zero. We form an orthogonal set of extended Hermite functions as a one-parameter family and use tensor products of the extended Hermite functions as building blocks in the fractional Wiener chaos expansion, in the same way that tensor products of Hermite polynomials are used as building blocks in the Wiener chaos polynomial expansion.
Estimating Cardiovascular Benefits of Tirzepatide in Sleep Apnea and Obesity: Insight from the SURMOUNT-OSA Trials
Authors: Beccuti Guglielmo , Bioletto Fabio , Parasiliti-Caprino Mirko , Benso Andrea , Ghigo Ezio , Cicolin Alessandro , Broglio Fabio
Published: October 2024

Purpose of Commentary

This commentary aims to offer a perspective on the effect of tirzepatide on hypoxic burden and provide indirect evidence of cardiovascular risk reduction after tirzepatide for the treatment of obstructive sleep apnea and obesity. It also discusses the role of tirzepatide-induced weight loss in the management of obstructive sleep apnea.

Recent Findings.

In the SURMOUNT-OSA phase 3 trials, tirzepatide, a new GIP/GLP-1 receptor co-agonist, reduced the apnea–hypopnea index, hypoxic burden, and body weight in adults with moderate-to-severe obstructive sleep apnea and obesity. The change in apnea–hypopnea index is clinically relevant, but its impact on cardiovascular mortality remains unclear. Conversely, hypoxic burden predicts cardiovascular mortality across populations independent of AHI.

We attempted to postulate the magnitude of cardiovascular benefits of tirzepatide based on the reduction in hypoxic burden. Tirzepatide treatment for obstructive sleep apnea and obesity seems to result in hypoxic burden values associated with a lower cardiovascular mortality rate and thus might attenuate the negative cardiovascular impact of hypoxic burden.
Differences in body dissatisfaction between individuals with and without stigma toward obesity: A study of preadolescents and adolescents
Authors: Amaya-Hernández Adriana , Ortega-Luyando Mayaro , Mancilla-Diaz Juan Manuel , Alvarez-Rayón Georgina , Cruz-Navarro Michelle , Pérez-Ortiz Alejandro
Published: October 2024

Introduction

Previous studies have focused on understanding the biopsychosocial implications of obesity stigma and have made proposals to minimize its negative consequences, as well as recommendations to eliminate or reduce this stigma; however, knowing which individuals stigmatize obesity and why will allow us to have a broader picture of stigmatization and thus help in planning interventions with greater impact.

Objective

The aims were to describe the stigmatization toward obesity in preadolescents and adolescents and to determine whether there are differences in body dissatisfaction, abnormal eating behaviors and self-esteem among those with and without stigma toward obesity.

Methods

A total of 307 preadolescents and 349 adolescents answered a set of questionnaires that evaluated abnormal eating behaviors, body dissatisfaction, self-esteem and stigma.

Results

Fifty-nine percent of the participants stigmatized individuals with obesity, with preadolescents having the greatest stigma levels. Differences were observed only in body dissatisfaction, where the group of preadolescents who stigmatized individuals with obesity and the group of adolescents who did not stigmatize individuals with obesity reported higher levels of body dissatisfaction.

Conclusion

Obesity is stigmatized at early ages, regardless of sex; however, preadolescents with stigma toward obesity and adolescents without stigma toward obesity have greater body dissatisfaction, indicating that body dissatisfaction plays a crucial role in the stigmatization of obesity.

Level of evidence

Level V, cross-sectional analytical study.
The LDI (Liability-driven Investment) Debacle, Derivatives and Systemic Risk: There You Go Again!
Authors: Bavoso Vincenzo
Published: October 2024

This article examines the role of derivatives in the context of the recent crisis in the UK pension system, specifically in liability-driven investment schemes. It unveils derivatives’ role as instruments that multiply and propagate losses among market participants once specific events (worst-case scenarios) materialise. This article questions the role of derivatives as risk-management and risk-diversification tools, given their employment, in this case as in others before, for speculative purposes. Critically, with speculation came higher than desirable levels of leverage that these financial products elicited, causing in the process a series of systemic concerns. While much criticism has been directed at post-2008 regulation, and particularly at clearing and margin requirements, this article proposes a broader view of the problems posed by derivatives in the different contexts of their applications. More specifically, attention is drawn to legal doctrines that could be redeployed for the purpose of mitigating the speculative nature of derivatives.
Martin Thrupp and Environmental Justice
Authors: Eames Chris
Published: October 2024

This personal reflection explores the strong thread of justice which coursed through Martin Thrupp and found expression through his connection to the environment and his local community. I relate how this expression touched not only his activism and advocacy, but also his academic work.
Polyline Morphing for Animated Schematic Maps
Authors: Forsch Axel , Kemna Ruben , Langetepe Elmar , Haunert Jan-Henrik
Published: October 2024

Thematic maps allow for the visual analysis of spatial data. When comparing two map states, preserving the mental map of a user facilitates the comparison. One way to achieve this is to use animated transitions between the states. This work presents an algorithm for computing such animations, called morphs, between schematized map objects, a technique particularly pertinent in urban mobility scenarios where schematic maps improve map legibility. In schematic maps, abstraction is used to reduce the visual complexity while still conveying information on a selected phenomenon. Our method ensures that the morph has four favorable properties: (1) it is self-intersection-free, (2) it maintains the schematization of the input features, (3) it is self-contained, and (4) every segment moves at its own constant velocity. We present an efficient algorithm to compute vertex traces and the timing of the morph. We evaluate our approach on isochrones visualizing travel times and on different layouts of schematic transit networks. The results show that the additional constraints we induce on the morphing only have a minor influence on the optimization target while they reduce the complexity of the animation.
Validation and Comparison of Non-stationary Cognitive Models: A Diffusion Model Application
Authors: Schumacher Lukas , Schnuerch Martin , Voss Andreas , Radev Stefan T.
Published: October 2024

Cognitive processes undergo various fluctuations and transient states across different temporal scales. Superstatistics are emerging as a flexible framework for incorporating such non-stationary dynamics into existing cognitive model classes. In this work, we provide the first experimental validation of superstatistics and formal comparison of four non-stationary diffusion decision models in a specifically designed perceptual decision-making task. Task difficulty and speed-accuracy trade-off were systematically manipulated to induce expected changes in model parameters. To validate our models, we assess whether the inferred parameter trajectories align with the patterns and sequences of the experimental manipulations. To address computational challenges, we present novel deep learning techniques for amortized Bayesian estimation and comparison of models with time-varying parameters. Our findings indicate that transition models incorporating both gradual and abrupt parameter shifts provide the best fit to the empirical data. Moreover, we find that the inferred parameter trajectories closely mirror the sequence of experimental manipulations. Posterior re-simulations further underscore the ability of the models to faithfully reproduce critical data patterns. Accordingly, our results suggest that the inferred non-stationary dynamics may reflect actual changes in the targeted psychological constructs. We argue that our initial experimental validation paves the way for the widespread application of superstatistics in cognitive modeling and beyond.
The first dimeric indole-diterpenoids from a marine-derived Penicillium sp. fungus and their potential for anti-obesity drugs
Authors: Du Hui-Fang , Li Lei , Zhang Ya-Hui , Wang Xu , Zhou Cheng-Yan , Zhu Hua-Jie , Pittman Charles U. , Shou Jia-Wen , Cao Fei
Published: October 2024

Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20–C-22′ linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1–3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs.
Correlation study of NF-κB, IER3, and Recurrence of Ovarian Endometrioid Cysts
Authors: Fan Xiang , Yang Ni , Huang Gu , Dong Yishan , Zhu Pengfeng
Published: October 2024

The study aimed to investigate the expression of nuclear actor-k-gene binding(NF-κB) and immediate early response 3(IER3) in ovarian endometrioid cysts and its correlation with the recurrence of the ovarian endometrioid cyst. From January 2018 to March 2019, a total of 88 patients who underwent laparoscopic ovarian cyst excision due to ovarian endometrioid cyst in Changzhou Maternity and Child Health Care Hospital were selected. Clinical data of the patients were collected. The patient's Revised American Fertility Society (R-AFS) score, least function(LF) score, and endometriosis fertility index (EFI) were calculated. Immunohistochemistry was performed to detect the expression of IER3 and NF-κB. The receiver-operating characteristic (ROC) curve was used to evaluate the predictive value of IER3 and NF-κB expression on postoperative recurrence. Cox regression was fitted to analyze the influencing factors of ovarian endometrioid cyst recurrence. The expression of NF-κB was positively correlated with IER3 (P < 0.001). ROC curve showed that NF-κB combined with IER3 had higher predictive value for disease recurrence. Multivariate Cox regression showed that the IER3 expression intensity > 4.5 (HR = 3.418,95%CI: 1.227 ~ 9.523, P = 0.019) and the NF-κB expression intensity > 4.5 (HR = 5.491,95%CI: 1.600 ~ 18.838, P = 0.007) were independent risk factors for recurrence, and EFI score (HR = 0.791,95%CI: 0.637 ~ 0.983, P = 0.035) was a protective factor for recurrence. Our results suggested that EFI score is a protective factor for recurrence. The expression levels of NF-κB and IER3 > 4.5 are correlated with the recurrence of ovarian endometrioid cysts and independent risk factors for recurrence.
Real-world insights into the management of hemophilia A in Italy: treatment patterns and healthcare resource utilization
Authors: Perrone Valentina , Leogrande Melania , Cappuccilli Maria , Esposti Luca Degli
Published: October 2024

Purpose

This real-world analysis described the Hemophilia A (HA) population in Italy, evaluating drug utilization and consumption of factor VIII (FVIII) products of patients under prophylaxis and on-demand therapy.

Methods

From Jan-2017 to Jun-2022, male patients with HA were identified through prescriptions of FVIII products [extended half-life FVIII, standard half-life recombinant FVIII, and plasma-derived FVIII (EHL FVIII, SHL rFVIII, and pdFVIII, respectively)], or emicizumab or FVIII plus von Willebrand factor or HA-related hospitalization using administrative flows of Italian healthcare entities. Patients on treatment with FVIII products during 2021–2022 were stratified by treatment regimen (prophylaxis/on-demand). The mean annual consumption expressed in International Units (IU) of EHL FVIII and SHL FVIII in patients treated during 2021–2022 having at least 12-month follow-up were assessed.

Results

Among included HA patients, 145 (39.5%) received EHL FVIII and 222 (60.5%) SHL FVIII. Of 165 patients on prophylaxis, 105 (64%) received an EHL FVIII and 60 (36%) an SHL FVIII. The mean annual consumption of FVIII was 336,700 IU (median 319,000 IU) for EHL FVIII and 440,267 IU (median 360,500 IU) for SHL FVIII. Specifically, for patients on EHL FVIII, the most common drugs were efmoroctocog alfa (N = 51) and damoctocog alfa pegol (N = 50), followed by turoctocog alfa pegol (N = 25) and rurioctocog alfa pegol (N = 19). Of 702 HA patients initially treated with FVIII products, 74 (10.5%) switched to emicizumab during follow-up.

Conclusion

These findings revealed an extensive use of EHL FVIII products, suggesting growing efforts from clinicians to optimize prophylactic strategies and achieve better bleeding protection.
A survey on LLM-based multi-agent systems: workflow, infrastructure, and challenges
Authors: Li Xinyi , Wang Sai , Zeng Siqi , Wu Yu , Yang Yi
Published: October 2024

The pursuit of more intelligent and credible autonomous systems, akin to human society, has been a long-standing endeavor for humans. Leveraging the exceptional reasoning and planning capabilities of large language models (LLMs), LLM-based agents have been proposed and have achieved remarkable success across a wide array of tasks. Notably, LLM-based multi-agent systems (MAS) are considered a promising pathway towards realizing general artificial intelligence that is equivalent to or surpasses human-level intelligence. In this paper, we present a comprehensive survey of these studies, offering a systematic review of LLM-based MAS. Adhering to the workflow of LLM-based multi-agent systems, we synthesize a general structure encompassing five key components: profile, perception, self-action, mutual interaction, and evolution. This unified framework encapsulates much of the previous work in the field. Furthermore, we illuminate the extensive applications of LLM-based MAS in two principal areas: problem-solving and world simulation. Finally, we discuss in detail several contemporary challenges and provide insights into potential future directions in this domain.