bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital twinning of vertical centrifugal casting
Authors: Anadkat Dhaval , Dave Anjali , Sata Amit , Shukla Minal , Jarboui Slaheddine
Published: November 2024

This paper explores the transformative potential of digital twin technology in vertical centrifugal casting (VCC), a cornerstone manufacturing process for high-integrity cylindrical components. By integrating real-time data, physical models, and machine learning algorithms, digital twins unlock a new paradigm of process optimization, predictive maintenance, and quality control. Integration of digital twinning enhances the performance in different domains of work like enhancing the quality of research, production etc. Howbeit, digital twinning is nascent in the domain of manufacturing specially in the casting sub domain. A physical set up of VCC is integrated with Internet of Things (IoT) and data acquisition system to stream the collected data to the cloud-based server. Transformation of Internet of Things (IoT) enabled VCC integrated with different sensors into the digital twin helps in quality prognosis for future applications. The data is further fetched from the cloud and interconnection is established between the digital twin. Real time monitoring, controlling and operating can be done easily with the help of a digital twin to predict the quality and tentative defect locations. Further amplifying these benefits, emerging technologies like Virtual Reality (VR), Augmented Reality (AR), and the Metaverse hold immense promise for revolutionising VCC training, collaboration, and visualisation.
The Effects of Climate Change Meta-Knowledge on Selective Exposure, Selective Elaboration, and Behavioral Intentions
Authors: Frauhammer Luna T. , Neubaum German
Published: November 2024

This experiment investigates how individuals’ meta-knowledge (the self-perception of one’s knowledge) influences selective exposure to and elaboration of information about climate change with climate change self-schema as possible mediator. Participants’ ( N = 510) meta-knowledge was manipulated by receiving fake feedback after a climate change knowledge test. There were no group differences in selective exposure and selective elaboration. Correlational evidence tentatively speaks for a “rich-get-richer” process of information selection and elaboration. This could be explained through climate change self-schemas which differed significantly between conditions ( d = 0.26) and correlated positively with selective exposure ( r = .36) and elaboration ( r = .28).
Safety Assessment of Wheat-Derived Ingredients as Used in Cosmetics
Authors: Burnett Christina L. , Bergfeld Wilma F. , Belsito Donald V. , Cohen David E. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Peterson Lisa A. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Fiume Monice , Heldreth Bart
Published: November 2024

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 wheat-derived ingredients. Most of these ingredients are reported to function as skin conditioning agents in cosmetic products. The Panel reviewed the available data to determine the safety of these ingredients. Industry should continue to use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that 21 wheat-derived ingredients are safe in cosmetics in the practices of use and concentration described in this safety assessment. However, the Panel also concluded that the available data are insufficient to make a determination of safety that the remaining six wheat-derived ingredients are safe under the intended conditions of use in cosmetic formulations.
Social motivations in Mapuche trafkintu: toward cosmology, recovery, and critique
Authors: Albersten Torben
Published: November 2024

This article investigates social motivations in trafkintu (exchange), a concept derived from the Mapuche (Indigenous people of southcentral Chile and southwestern Argentina: literally, people of the land). We propose five key motivations for trafkintu, reciprocity, solidarity, cosmological, recovery, and critique. While reciprocity and solidarity are commonly associated with exchanges, we argue that from a Mapuche perspective it is essential also to relate them to a cosmological motivation, something often neglected by the anthropocentric focus of Western academics. The motivations of recovery and critique reject the idea that Indigenous economical concepts only explain the past by considering the contemporary context of trafkintu. Recovery and critique testify to the colonial economic onslaught and the difficulty of reproducing the motivations of reciprocity, solidarity, and cosmology within a market-driven economy. Recovery and critique motivate trafkintu as a heterodox economic institution with strategic similarities to other anti-hegemonic forces, making them potential allies.
Trends of Pathological Findings in Patients with Thyroid Diseases: A Single-center, Retrospective Study
Authors: Naseem Masooma , Ali Sajjad , Qadir Sara , Riaz Anshahrah , Monawwer Abdullah , Tahir Burhanuddin , Naseem Zehra , Mehmood Zahid
Published: November 2024

Background:

Globally, a rising trend has been observed in the prevalence of thyroid disorders, with many demographic and geographic factors influencing its epidemiology. Nonetheless, some cases often go undetected due to the inconsistent and non-specific nature of the clinical symptoms. Therefore, we aimed to determine the trend and relationship between various pathological findings in thyroid disease patients and their demographic factors to aid clinicians in making a prompt diagnosis and treatment plan.

Methods:

A descriptive correlational study was conducted from January 2020 to May 2022 at Jinnah Postgraduate Medical Center, Karachi. We collected data via random sampling from 258 patients suffering from thyroid disorders. We evaluated baseline patient characteristics, along with, thyroid scan and fine needle aspiration cytology (FNAC) reports, and local thyroid gland examination findings.

Results:

Out of 258 participants, 192 (74.4%) were females, whereas 66 (25.6%) were males, giving a female: male ratio of 2.9: 1. On local examination, 167 (64.7%) were found to have a solitary nodule, 79 (30.6%) had multinodular goiter. Findings revealed that benign follicular lesions had the highest prevalence (35.3%). Moreover, among the cancerous growth, papillary carcinoma presented the highest cases (12.4%). Of 258 cases, 24 patients had non-surgical interventions, while most (234) had surgical interventions. Total thyroidectomy was the most common procedure opted for by 45.3% (n = 117) of the participants, followed by lobectomy 70 (27.1%), near total thyroidectomy 43 (13.2%), modified radical neck dissection 5 (1.9%).

Conclusion:

Our study showed that nearly all thyroid-related pathologies were more prevalent amongst females than males, with the majority having an acute to sub-acute clinical presentation. Multinodular goiter was a prominent finding indicating a greater need for screening tools and access to healthcare facilities, especially in rural areas, to allow future studies to compare provinces accurately.
Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies
Authors: Carvajal René , Rodríguez-Acevedo Breogán , García-Vasco Lorena , Zabalza Ana , Ariño Helena , Bollo Luca , Cabello-Clotet Noemí , Castilló Joaquín , Cobo-Calvo Álvaro , Comabella Manuel , Falcó-Roget Anna , Galán Ingrid , García-Sarreón Alexis , Gómez-Estévez Irene , Granados Galo , La Puma Delon , Mato Chain Gloria , Midaglia Luciana , Nieto-García Asunción , Otero-Romero Susana , Pappolla Agustín , Rodriguez Marta , Sansano Irene , Río Jordi , Tagliani Paula , Tur Carmen , Vidal-Jordana Ángela , Vilaseca Andreu , Villar Ana , Sastre-Garriga Jaume , Oreja-Guevara Celia , Tintoré Mar , Montalban Xavier , Arrambide Georgina
Published: November 2024

Background:

Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited.

Aim:

To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20.

Methods:

Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023.

Results:

Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID.

Conclusions:

In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.
Lost and found: Investigating a bilingual child’s L1 lexical attrition and recovery
Authors: Lee Sunyoung , O’Grady William
Published: November 2024

Aims and Objectives:

We examined the extent of L1 vocabulary attrition in a Korean child following her relocation to the United States at the age of 6 years 10 months, and the subsequent restoration of her L1 vocabulary upon her return to Korea 10 months later.

Methodology:

A picture-naming task was administered on a regular basis over a period of several months, beginning shortly after the child’s arrival in the United States.

Data and Analysis:

The data were analyzed to determine the child’s accuracy in producing common nouns in the L1.

Findings/Conclusion:

The study shows significant L1 vocabulary attrition after just 1 month, with an inability to access half of the test items after just 4 months and a drop in accuracy to 25% after 9 months. Upon return to Korea, the child’s L1 vocabulary improved rapidly, surpassing English usage within 3 weeks and reaching 82% accuracy within 6 weeks. These findings underscore the vulnerability of children to language attrition in a monolingual environment while also highlighting the remarkable resilience of their L1 skills.

Originality:

The study traced the child’s L1 decline and recovery in accordance with a strict timetable. By beginning measurements within a week of the child’s exposure to English following her subsequent reintroduction to Korean, the study was able to document the earliest manifestations of lexical attrition, its rapid progression, and its subsequent reversal—a pattern of decline and recovery that is rarely studied in this manner.

Significance/Implications:

This study contributes to the field by systematically documenting the impact on L1 vocabulary of a sudden change in linguistic environment, providing rare insights into the dynamics of lexical attrition in early bilingualism.
An analysis of estimation strategies for knock control
Authors: Peyton Jones James C. , Patel Vatsal , Frey Jesse
Published: November 2024

Since knock behaves as a random process, all knock controllers regulate some statistical property of this process which must be estimated from the data. The choice of the statistical metric used for feedback, its target value, and the method used for its estimation all have a strong impact on the performance of the closed loop system. In this work, expressions for the asymptotic variance of the estimates of different test statistics are derived and used to compare empirical versus parametric estimation methods. The variance of different metrics and the slope of their response curves (e.g. knock probability vs knock percentile intensity feedback) are also used to compute and compare the efficacy of these different measures for knock control purposes. The efficacy is seen to vary as a function of the chosen knock probability target, and lower knock thresholds/higher knock rate targets are recommended. Finally, the estimator dynamics are shown to dominate the dynamics of the closed loop response, and estimates obtained using a sliding window versus an exponentially weighted moving average are compared and contrasted. In each case, the results are illustrated using closed loop simulations of controller response subject to disturbances.
Acquiring intuitive knowledge: A response to Nadler
Authors: James Susan
Published: November 2024

In this response to Steven Nadler’s paper, I ask whether Spinoza views the transition from rational to intuitive knowledge as an individual or a collective project and conclude that it is largely a collective one. For Spinoza, our individual capacity to reason is underwritten by a social practice, an art of reasoning, which licences the rational conclusions on which intuitive knowledge rests. Equally, the pursuit of intuitive knowledge rests on a shared art of intuiting. Both kinds of knowledge are therefore collective achievements. If this is right, acquiring intuitive knowledge presupposes a certain kind of education. While it may be in principle available to everyone, as Nadler claims, it depends in practice on educational luck.
Maimonides and Spinoza on perfection in knowing and affect
Authors: Klein Julie R.
Published: November 2024

This article develops the ideas of perfection and education in Spinoza and Maimonides. Both thinkers identify human perfection with intellectual knowledge and a transformation in affect. They accordingly envision education in terms of enhancing cognition and shaping the desire to know. The first steps are a critical evaluation of imagination and the development of the mind’s rational, inferential powers. These steps stabilize and strengthen our positive affects, and they arouse a desire for what Spinoza calls the third kind of knowing and Maimonides calls intellectual apprehension. Individuals achieve this highest perfection by degrees, if at all. Spinoza argues that the more the body can undergo, the more we know, the more active and hence the more perfect we are, and the more joy, love, and satisfaction we experience. Spinoza calls the third kind of knowing both scientia intuitiva and amor dei intellectualis. Maimonides’s perfect human being experiences an intellectual apprehension of the existence of God and receives flashes of insight concerning aporetic metaphysical questions. Although Spinoza’s amor dei intellectualis transforms the knower’s way of living, it is not explicitly political. Maimonides’ model of the perfect human is Moses, whose intellectual apprehension brings about a passionate love for God and eventuates in prophecy, which Maimonides theorizes as the overflow of intellectual attainment through imagination. Moses is the most perfect prophet, the one who founds and organizes a community.
Sources of Legitimacy in Participatory Budgeting: A Scoping Review
Authors: Bernhard Laurent , Hänggli Fricker Regula , Wellings Thomas , Pournaras Evangelos
Published: November 2024

This article conducts a scoping review to explore the key determinants of political legitimacy in participatory budgeting. The scoping review employs a comprehensive search of Scopus to select relevant studies. Three main sources of legitimacy emerge from this analysis: (1) institutions, (2) citizen participation, and (3) deliberation. The findings reveal that participatory budgeting can significantly affect political legitimacy through these mechanisms. In addition, the study highlights the relevance of legitimacy, as it relates to participatory budgeting, in both democratic and non-democratic contexts, with particular attention to participatory budgeting practices in China.
Controversial Cartoon at Central University
Authors: Victor Jasmine , Wengelnik Cate
Published: November 2024

This fictional case study provides a summary of events that took place at Central University after the campus newspaper published a controversial political cartoon mocking media coverage of the killing of an unarmed Black man. The cartoon and lack of administrative response led to the formation of a student activist group. The case highlights the conflict some campus administrators perceive in protecting student expression, which may harm other students’ feelings of safety and belonging. Discussion questions and suggested class activities are included.
Bioinformatics Combined With Experimental Modeling to Study the Molecular Mechanism of Xuefu Zhuyu Decoction to Improve Erectile Dysfunction Associated With Asthma in Rats
Authors: Feng Junlong , Deng Sheng , Gong Xuefeng , Wang Bin , Sun Longji , Zhang Huanan , Gao Zixiang , Chen Hui , Zou Kali , Yang Jiaqi , Li Haisong , Wang Jisheng
Published: November 2024

Asthma is associated with chronic systemic inflammation, and inflammatory factors can damage vascular endothelial cells, thus impairing erectile function (ED). Xuefu Zhuyu decoction (XFZYD) can inhibit inflammation and promote angiogenesis, which in turn improves asthma as well as ED, but its exact mechanism of action is not yet clear. This study investigates the mechanism underlying the beneficial effect of XFZYD on asthma-associated ED. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze the constituents of XFZYD, and network pharmacology analysis was used to predict the target genes of XFZYD. Sprague–Dawley rats in the asthma model with erectile dysfunction were divided into the model, XFZYD low-, medium-, and high-dose group (3.09, 6.17, and 12.34 g/kg), with drug intervention for 8 weeks. We assessed the interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), and tumor necrosis factor (TNF) protein levels in the penile tissue. We discovered that after treatment with XFZYD (3.09, 6.17, and 12.34 g/kg), the number of erections significantly increased (1.17 ± 0.41, 1.50 ± 0.55, and 1.67 ± 0.52), the density of endothelial cells in the corpus cavernosum of the penis increased, the expression level of IL-6 was reduced (7.5%, 21.2%, and 24.4%), the expression level of VEGFA was reduced (7.8%, 25%, and 28.4%), and the expression level of TNF was reduced (13.5%, 30.6%, and 32.4%). The in vivo experiments indicate that XFZYD may improve ED in asthma model rats by inhibiting inflammation and reducing vascular permeability. This study provides new insights into the mechanism of action of XFZYD in the treatment of asthma leading to ED.
Tracing Implicit Knowledge in Professional Milieus: Methodological Reflections on the Analysis of Theorizing Accounts
Authors: Schmidt Franziska
Published: November 2024

The exploration of what lies beyond the explicitly expressed is a challenge for qualitative research. It involves studying something that is not directly given. This paper presents different methodological solutions and focuses on implicit knowledge in professional contexts and theorizing accounts. I will discuss conceptualizations of tacit knowledge and implicit learning, and then focus on specific aspects of the Documentary Method. The Documentary Method is a research strategy that attempts to explicate implicit collective orientations through group discussions. It is based on Karl Mannheim’s sociology of knowledge and aims to uncover the taken-for-granted mutual understanding that results from shared or similar experiences. Based on Mannheim’s critique of rationalism, this understanding is assumed to be found in the narrative and descriptive parts of group discussions. However, this article examines whether it can also be found in theorizing accounts. It draws on Hans Blumenberg’s insight that metaphors are often contained in technical language and can obscure an underlying system of orientation. In this case, implicit mutual understanding is based on shared or similar experiences that are difficult to fully understand and articulate. An illustrative interpretation of data from a team specializing in sexuality education demonstrates the practical application of these methodological considerations. In essence, the article addresses the question of how implicit knowledge emerges in language and provides a new lens for analyzing theorizing accounts.
Pragmatic monitoring of emerging efficacy data in randomized controlled trials
Authors: Bangdiwala Shrikant I , Yusuf Salim
Published: November 2024

Monitoring the conduct of phase III randomized controlled trials is driven by ethical reasons to protect the study integrity and the safety of trial participants. We propose a group sequential, pragmatic approach for monitoring the accumulating efficacy information in randomized controlled trials. The “Population Health Research Institute boundary” is simple to implement and sensible, as it considers the reduction in uncertainty with increasing information as the study progresses. It is also pragmatic, since it takes into consideration the typical monitoring behavior of monitoring committees of large multicenter trials and is relatively easily implemented. It not only controls the overall Lan–DeMets type I error probability (alpha) spent, but performs better than other group sequential boundaries for the total nominal study alpha. We illustrate the use of our monitoring approach in the early termination of two past completed trials.
The effect of an enhanced fetal growth ultrasound protocol on pregnancy outcomes: A retrospective service evaluation within a single UK National Health Service centre between 2014 and 2022
Authors: Butterfield Eleanor , Skelton Emily
Published: November 2024

Aim:

Growth Assessment Protocol is a fetal growth initiative designed to improve antenatal detection of babies who are small-for-gestational-age and reduce stillbirths. However, its direct impact on pregnancy outcome and stillbirth rates is questioned. This service evaluation aimed to assess Growth Assessment Protocol’s influence on pregnancy outcomes at a National Health Service hospital.

Method:

Anonymous, maternity and ultrasound data, routinely acquired between 2014 and 2022 were extracted from clinical databases (Viewpoint, Euroking). Trends in maternity data and ultrasound scan volume were explored with descriptive statistics. Variables of stillbirth, antenatal small-for-gestational-age detection and scan volume were compared before and after Growth Assessment Protocol implementation. Associations between these variables were evaluated using Spearman’s rho.

Results:

The percentage of babies born small-for-gestational-age reduced by 0.3% across the evaluation period. Antenatal small-for-gestational-age diagnosis rose from 4.1% to 14.3%. However, the number of false-positive cases of antenatally diagnosed small-for-gestational-age increased fivefold from 2.2% to 11.5%. Although stillbirth rates remained consistent post-Growth Assessment Protocol, complex scan volume (e.g. number of growth scans using Doppler) increased annually. The peak incline coincided with the Growth Assessment Protocol implementation period (2016–2018). Complex scan volume was significantly associated with overall small-for-gestational-age detection (rho = 0.8, p =< 0.001), but not with stillbirth frequency (rho = −0.1, p = 0.4).

Conclusion:

Small-for-gestational-age detection increased following Growth Assessment Protocol implementation, although this was associated with a high false-positive rate and no reduction in stillbirths. The potential implications associated with clinical management, parent experiences and departmental workflow, alongside the benefits for stillbirth reduction, should be fully considered prior to the introduction of a new fetal growth initiative to the antenatal care pathway.
Disorders of puberty
Authors: Mantova Maria Chiara , Garcia Verstraete Marie Astrid
Published: November 2024

Puberty is a critical developmental phase marking the transition from childhood to adulthood, characterised by physical, hormonal and psychological changes. Disorders of puberty can have a significant impact on a person’s growth, development, and psychological well-being. These disorders can cause precocious (early onset) or delayed (late onset) puberty and necessitate a thorough understanding of the underlying mechanisms and clinical presentation to ensure proper diagnosis and treatment. This article provides a comprehensive overview of the hypothalamic–pituitary–gonadal axis and adrenal development leading to physical changes consistent with puberty. This article outlines the physiological physical changes and pubertal milestones and discusses normal variants of puberty to help distinguish physiological from pathological conditions. It then describes the pathophysiology and causes for both precocious and delayed pubertal development, providing guidance for primary care physicians for referral to secondary care. Finally, this article aims to provide succinct guidance on relevant history and clinical findings pertinent to the topic and provides a clinical case for discussion.
Bacterial signature in retrieved thrombi of patients with acute ischemic stroke—a systematic review
Authors: Zarrintan Armin , Ghozy Sherief , Thirupathi Kasthuri , Walden Kalah , Brinjikji Waleed , Kallmes David F. , Kadirvel Ramanathan
Published: November 2024

Background:

Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS.

Objectives:

We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS.

Design:

This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.

Data sources and methods:

A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies.

Results:

The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed.

Conclusion:

Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.
Therapy-relevant MDM2 amplification in cholangiocarcinomas in Caucasian patients
Authors: Lyu Su Ir , Plum Patrick Sven , Fretter Caroline , Simon Adrian Georg , Bedau Tillmann , Knipper Karl , Thomas Michael N. , Stippel Dirk , Wagner Britta Janina , Bruns Christiane , Waldschmidt Dirk , Büttner Reinhard , Drebber Uta , Quaas Alexander
Published: November 2024

Background:

Cholangiocarcinomas (CCA) are a group of aggressive malignancies with poor prognosis. The distinct subtypes are related to different etiologies and genetic aberrations that are subject to targeted therapies. Mouse double minute 2 homolog (MDM2) is a potent inhibitor of tumor suppressor p53 and is proven to be altered in certain carcinomas. Novel targeted drugs, such as the MDM2-p53 antagonist Brigimadlin, have shown promising results for therapeutic efficacy in patients with MDM2 amplification and wild-type TP53.

Objectives:

This study therefore aimed to characterize CCAs regarding their MDM2 status, compare the concordance between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods, and elucidate the role of MDM2 amplification in prognosis and other clinicopathological characteristics.

Design:

Retrospective cohort study.

Methods:

All patients ( n = 52) were diagnosed with CCA and received surgical resection with curative intention at the University Hospital of Cologne. Samples were analyzed retrospectively for MDM2 amplification with FISH and IHC. We correlated results with pre-existing molecular as well as clinical data.

Results:

We included 52 patients with primary CCA, three of which showed positive MDM2 amplification (5.8%). MDM2 amplification was present only in the intrahepatic CCA type and all patients with positive MDM2 amplification exhibited normal p53 status. Among the large-duct subtypes of intrahepatic CCAs, patients with positive MDM2 amplification demonstrated better survival than patients with negative MDM2 amplification ( p = 0.041). Of the patients with MDM2 amplification, two underwent adjuvant therapy post-surgery (66.7%). There was a strong correlation between MDM2 amplification and positive protein expression in IHC. There were no identifiable molecular co-alterations of MDM2 with FGFR2 or SWI/SNF complex alterations.

Conclusion:

Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA.
Cost-effectiveness of acalabrutinib monotherapy or with obinutuzumab versus chemoimmunotherapy for untreated chronic lymphocytic leukemia in China
Authors: Li Mengya , Zhong Xiaoyan , Zhang Chengbin , Luo Hongli , Luo Li , Huang Yilan , Jiang Longyang
Published: November 2024

Background:

Acalabrutinib is a highly selective, latest generation Bruton’s tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia (CLL). The ELEVATE-TN trial (NCT02475681) found significant benefits achieved by the acalabrutinib regimen compared to the chemoimmunotherapy regimen chlorambucil plus obinutuzumab in treatment-naïve CLL. The objective of this study was to explore the cost-effectiveness of acalabrutinib in the first-line treatment of CLL in the light of Chinese healthcare system.

Methods:

We constructed a 4-week partitioned survival model and a 20-year lifetime horizon to estimate the cost and utility associated with CLL treatment. The survival data, direct medical costs, and utilities came from the ELEVATE-TN trial, YAOZHI database, and published literatures. The outputs of the model including total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity, and scenario analyses were conducted to assess the robustness of the model.

Results:

Over a 20-year lifetime horizon, treatment with acalabrutinib + obinutuzumab provided an additional 2.51 QALYs versus treatment with chlorambucil and obinutuzumab, while incurring incremental costs of $940,543 and an ICER of $374,449/QALY. Acalabrutinib had an incremental cost of $683,640 and provided an additional 2.24 QALYs, resulted an ICER of $305,562/QALY. One-way sensitivity analyses suggested that the model was most sensitive to utility of progression-free survival, progression disease, and the cost of acalabrutinib. Probabilistic sensitivity analyses showed that at the willingness-to-pay (WTP) threshold, the probabilities of the acalabrutinib regimens were at an absolute disadvantage. The scenario analyses showed altering the lifetime horizon or price of acalabrutinib did not reverse results of our model.

Conclusion:

Acalabrutinib with or without obinutuzumab might not be a cost-effective option in recent China, when compared with chemoimmunotherapy for first-line patients with CLL at the commonly WTP threshold. It is therefore necessary to reduce the price of acalabrutinib.
Identifying CNS infections in transplantation and immunomodulatory therapy
Authors: Alviz Luisa F. , Jones Benjamin A. , Agnihotri Shruti P. , Thakur Kiran T.
Published: November 2024

Opportunistic central nervous system (CNS) infections are a significant cause of morbidity and mortality in immunocompromized patients, including those undergoing transplantation and receiving immunomodulatory therapy. Particularly in these individuals, the clinical presentation of these infections may have atypical patterns, emphasizing the need to consider various diagnostic possibilities, including noninfectious conditions. Quick and accurate identification, along with prompt treatment, is crucial for improving patient outcomes. Therefore, understanding which pathogens are likely to cause infection based on factors such as timing post-transplantation, specific organ transplant, and the mechanism of action of immunomodulatory medications is essential. This review will provide a detailed description of the types of infections that may arise in the context of transplantation and immunomodulatory therapy.
The economic burden of leprosy treatment to households in Ghana: A cross-sectional study in the Volta Region of Ghana
Authors: Dalaba Maxwell Ayindenaba , Manyeh Alfred Kwesi , Immurana Mustapha , Ayanore Martin Amogre , Agorinya Isaiah , Akazili James , Akweongo Patricia , Quao Benedict Okoe
Published: November 2024

Background:

Despite the known detrimental socio-economic consequences of leprosy morbidity, disability and social exclusion at the household level, research investigating the precise economic burden of leprosy remains scarce. This study aims to address this gap by examining the socio-economic burden of leprosy in Ho municipality in the Volta Region of Ghana.

Methods:

This was a cross-sectional cost of illness study, and quantitative data were collected from leprosy patients between October and December 2023. Data collected included socio-demographic characteristics, direct and indirect costs related to treatment of leprosy from the patient’s perspective. Stata version 14 was used for the analysis.

Results:

A total of 35 respondents participated in the study, comprising 51.43% females and 48.57% males. All respondents (100%) reported having a valid National Health Insurance Scheme membership. The average total cost of leprosy treatment per patient, encompassing both direct and indirect expenses, was US$361.54 (SD ± 286.87). Disaggregating this cost further revealed a medical cost of US$44.30, a non-medical cost of US$47.07 and an indirect cost of US$290.16. The estimated annual household income of respondents was US$446.4 and 60% of respondents incurred expenditure that was more than 10% of their annual income and were deemed to have experienced catastrophic payment. Patients with sequelae incurred additional costs of US$46 (range: US$8.3–US$166.7) per case.

Conclusion:

The costs of treating leprosy were considerably high leading to catastrophic health payments. This highlights the need for an all-encompassing strategy that addresses medical, non-medical and indirect costs. Implementing targeted support programs and ensuring medication affordability are key steps towards mitigating the economic susceptibility of leprosy patients and facilitating successful treatment outcomes.
Determinants of satisfaction with community-based health insurance schemes among beneficiaries with chronic diseases in selected public hospitals in Eastern Ethiopia: A multicenter study
Authors: Mohammed Yoniso , Birhanu Simon , Abdu Kadir , Ahmed Nesredin , Letta Shiferaw
Published: November 2024

Background:

Community-based health insurance is a voluntary scheme where community members pool resources to cover healthcare costs. Assessing beneficiary satisfaction with chronic disease management is crucial for the program’s long-term viability. Therefore, this study aimed to assess determinants of satisfaction with community-based health insurance among beneficiaries with chronic diseases in selected public hospitals in the Hararghe Zones of Eastern Ethiopia.

Methods:

An institution-based cross-sectional study was conducted among randomly selected 416 chronic disease beneficiaries of community-based health insurance from 30 July to 30 August 2023. Data were collected through a pre-tested and structured face-to-face interview questionnaire. The data were entered into Epi-Data 3.1 and then exported to STATA 17.0 for analysis. Bivariate and multivariate logistic regression analyses were performed to identify determinants of satisfaction with community-based health insurance. Significance was set at a p-value < 0.05.

Results:

The mean age of the study participants was 48.10 ± 15.8 years. The study revealed that 55.1% (95% CI: 50.2%–59.8%) of beneficiaries with chronic diseases were satisfied with community-based health insurance. Beneficiaries aged over 55 years (AOR = 0.27; 95% CI: 0.08–0.91), experiencing delayed community-based health insurance opening times (AOR = 0.35; 95% CI: 0.17–0.73), preferring hospitals for future services (AOR = 4.13; 95% CI: 1.14–14.85), shorter waiting times (<60 min) (AOR = 8.8; 95% CI: 4.39–17.72), availability of drugs (AOR = 2.67; 95% CI: 1.30–5.45), availability of laboratory services (AOR = 5.5; 95% CI: 2.83–10.84), and knowledge of community-based health insurance benefit packages (AOR = 2.8; 95% CI: 1.47–5.43) were significant determinants associated with satisfaction to the community-based health insurance service.

Conclusion:

About half of the community-based health insurance beneficiaries with chronic diseases were satisfied, indicating that a considerable number of them were dissatisfied with the services. The age of the participants, office opening time, waiting times, laboratory services, pharmacy services, and knowledge of community-based health insurance benefit packages were significant determinants of satisfaction with community-based health insurance schemes. Therefore, the government and other stakeholders need to enhance service quality, increase awareness, and address both supply and demand-side factors. These key strategies can lead to higher satisfaction with and ensure the sustainability of community-based health insurance schemes.
The long noncoding RNA MIR4435-2HG enhances the migration, promotion, and glycolysis of nonsmall cell lung cancer cells by targeting the miR-371a-5p/SOX2/PI3K/Akt axis
Authors: Yang Jin , Su Yu , Wang Yuchen , Gao Kun , Li Chuang , Li Mengmeng
Published: November 2024

Background:

Nonsmall cell lung cancer is a leading cause of cancer-related death worldwide. The long noncoding RNA MIR4435-2HG has been shown to play a carcinogenic role in various cancers. The purpose of this study was to explore the role and regulatory mechanism of MIR4435-2HG in non-small cell lung cancer.

Methods:

Quantitative real-time polymerase chain reaction was used to detect MIR4435-2HG and SRY-box transcription factor 2 in nonsmall cell lung cancer cells. Gain- or loss-of-function assays of MIR4435-2HG and SRY-box transcription factor 2 were subsequently conducted. Cell proliferation, apoptosis, migration, glycolysis, and invasion were tested. A nude mouse tumor model was constructed to determine the role of MIR4435-2HG and SRY-box transcription factor 2 in the growth of tumor cells in vivo. Furthermore, the interactions between MIR4435-2HG, miR-371a-5p and SRY-box transcription factor 2 were analyzed via a dual-luciferase reporter gene assay.

Results:

Quantitative real-time polymerase chain reaction revealed that MIR4435-2HG and SRY-box transcription factor 2 were upregulated in nonsmall cell lung cancer cells. Forced MIR4435-2HG overexpression led to increased cell proliferation, migration, invasion, and glycolysis and repressed cell apoptosis. Overexpressing MIR4435-2HG promoted SRY-box transcription factor 2 expression and PI3K/Akt/mTOR pathway activation. Downregulating MIR4435-2HG had antitumor effects both in vitro and in vivo. SRY-box transcription factor 2 overexpression mostly reversed the suppressive effects of MIR4435-2HG downregulation. Mechanistic studies revealed that MIR4435-2HG, a competitive endogenous RNA, directly targeted and inhibited miR-371a-5p. Rescue assays revealed that miR-371a-5p overexpression or SRY-box transcription factor 2 downregulation significantly inhibited MIR4435-2HG-mediated oncogenic effects.

Conclusion:

MIR4435-2HG promotes nonsmall cell lung cancer cell malignant behaviors and glycolysis by regulating the miR-371a-5p/SOX2 axis.
A nursing-led sepsis response team guiding resuscitation with point-of-care ultrasound: A review and model for improving bundle compliance while individualizing sepsis care
Authors: Nunnally Jared , Ko So Mi , Ugale Kristen , Lowe Tammy , Bond Jaclyn , Kenny Jon-Emile S , Fargo Ramiz A , Haycock Korbin
Published: November 2024

A dysregulated host response to infection resulting in life-threatening organ dysfunction defines the onset of sepsis. Unfortunately, sepsis is common, costly, and deadly. The Surviving Sepsis Campaign publishes regularly updated, evidence-informed, detection, and treatment guidelines culminating in time-sensitive care “bundles.” The goal of these bundles is to expedite sepsis recognition because it is widely held that early treatment is life-saving. Hospitals are mandated to publicly report their bundle compliance, and this will soon be tied to hospital reimbursement. For these reasons, hospitals are creating sepsis emergency response teams which are a form of a rapid response team consisting of dedicated medical professionals who evaluate patients with suspected sepsis and initiate therapy when appropriate. Evidence to date support sepsis emergency response teams as a mechanism to improve bundle compliance, and potentially, patient outcome. Nevertheless, some elements of bundled sepsis care are controversial (e.g., intravenous fluid administration) as some argue that mandated treatment precludes personalized care. Herein, we briefly describe general sepsis emergency response team structure, review evidence supporting sepsis emergency response teams to improve bundle compliance and patient outcome and report our unique experience incorporating point of care ultrasound—to guide intravenous fluid—into a nursing-led sepsis team. We propose that our sepsis emergency response team approach allays concern that sepsis care is either bundled or personalized. Instead, incorporating point of care ultrasound into a nursing-led sepsis emergency response team increases bundle compliance and individualizes care.
Factors influencing in-hospital mortality in cancer patients with COVID-19: A retrospective survival analysis
Authors: Amado-Garzón Sandra Brigitte , Molina-Pimienta Luisana , Vásquez-Jiménez Juan Manuel , Álvarez-Raigoza Karen Lizeth , Manrique-Samer Mauricio , Lombo-Moreno Carlos E , Cañas-Arboleda Alejandra
Published: November 2024

Objective:

The aim of this study was to evaluate survival in patients with COVID-19 and cancer, and to find factors associated with early mortality.

Methods:

Retrospective cohort derived from a registry of a referral center in Bogotá. Survival was analyzed according to the type of neoplasm using Kaplan–Meier method. A cox regression was performed to look for factors associated to higher risk of death.

Results:

Two hundred fifty-four patients were included with cancer and COVID-19, most of whom were women (median age 68 years; range 19–97). Cardiovascular comorbidities were frequent. Patients with hematologic neoplasms had higher survival than those with solid neoplasms (log-rank test, p = 0.024). C-reactive protein levels (hazard ratio 1.02; 95% confidence interval 1.00–1.03, p = 0.025), Charlson’s comorbidity index (hazard ratio 1.15; 95% confidence interval 1.06–1.26, p = 0.004) and respiratory failure (hazard ratio 4.83; 95% confidence interval 2.47–9.44, p = <0.001) were significantly associated with higher mortality. No interaction between active anticancer therapy and mortality was observed.

Conclusion:

In contrast to other reports, survival was worse in patients with solid tumors than in those with hematologic neoplasms. Increased C-reactive protein, Charlson’s comorbidity index and respiratory failure were associated with higher in-hospital mortality. This study reveals the complex impact of cancer and its treatment on COVID-19 outcomes, highlighting the persistent risks to cancer patients. It emphasizes monitoring C-reactive protein levels, comorbidities, and respiratory failure as key indicators of poor prognosis. Furthermore, we provide new insights into the differential impact of COVID-19 on cancer patients with solid organ versus hematologic neoplasms.
The AI Chatbot Always Flirts With Me, Should I Flirt Back: From the McDonaldization of Friendship to the Robotization of Love
Authors: Lin Bibo
Published: November 2024

How is the use of artificial intelligence (AI) technologies, such as machine learning (ML) algorithms and Large Language Models (LLMs), in social chatbots transforming friendship and love? This study investigates Replika, an app offering AI friends and/or lovers to users. Unlike most AI companion research grounded in Human-Machine Interaction (HMI) and interpersonal communication theories, this study employs the sociological concept of McDonaldization to interrogate broader social and cultural implications of Replika. I argue that McDonaldization offers a systematic framework to understand the fast friendship and fast love provided by social chatbots while accounting for its limits in addressing the personalization enabled by emerging AI technologies. To bridge the conceptual gap, I propose the term “Robotization of Love,” pointing to the merging of efficient, quantifiable, predictable, and controllable love and algorithmically personalized love. The Robotization of Love also underscores the growing significance of robotic elements in shaping our affection and sociality.
Global Research Trend of Sustainable Transport in Response to Energy Efficiency: A Bibliometric Analysis
Authors: Asha’ari Maryam Jamilah , Daud Salina , Kasavan Saraswathy , Wan Abdullah Wan Mohammad Taufik , Mustapa Siti Indati , Rajadurai Jegatheesan , Ahmad Nurul Nadiah , Wan Hanafi Wan Noordiana , Toolib Siti Norhidayah , Mohamed Ali Mohamed Azrin bin
Published: November 2024

Numerous studies have been conducted on sustainable transportation and its impact on global energy efficiency. However, the evolution and performance patterns of this field remain relatively unknown and limited. A bibliometric analysis was conducted to explore the global research trends to determine the state-of-the-art sustainable transport linked to energy efficiency over the past 21 years. The Web of Science (WoS) database was searched to explore the research related to sustainable transport in response to energy efficiency from 2002 to 2022, resulting in the identification of 2,884 articles. In this study, VOSviewer was used to analyse collaboration networks between authors, countries, institutions and co-occurrence analysis of keywords in three defined periods. The results reveal that the majority of studies on sustainable transport and energy efficiency were primarily conducted in the USA, with limited research conducted in Asian countries. The study found that the subject categories of “transport planning,”“transport policy,”“climate change,”“electric vehicles,” and “public transport” are the most prolific research contributors. During Phase III (2016–2022), most studies were centred around electric vehicles in the field of sustainable transportation, as opposed to Phase II (2009–2015). These findings enhance our understanding of the research landscape in this field and offer valuable insights for future studies. Future studies could examine how the latest technology enhances energy efficiency in the transportation sector and focus on the usage and benefits of hydrogen fuel cell vehicles (HFCVs).