bluuebunny/crossref_metadata_2025 huggingface dataset:
Placental neutrophil reverse trans-migration and maternal serum neutrophil extracellular trap expression in HIV infection co-morbid pre-eclampsia in women of African ancestry
Authors: Moodley Merantha , Moodley Jagidesa , Naicker Thajasvarie
Published: June 2024

Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role of the comorbidity of PE and human immunodeficiency virus (HIV) infection in placental neutrophil r-TM and serum NETs remains unknown. Human placental tissue (n = 160) and serum (n = 80) samples were obtained post-ethical approval and divided by pregnancy type and HIV status and across the study population. Immunohistochemistry and morphometry were performed to localize and quantify junctional adhesion molecule-C (JAM-C) expression as an inverse marker of neutrophil r-TM within placental villi. An enzyme-linked immunosorbent assay (ELISA) was performed to quantify the concentration of citrullinated histone H3 (cit-H3) as a marker of NETs. GraphPad Prism (version 8.0.2) was used to compare the results, and a p value of p < 0.05 was considered statistically significant. The localization of JAM-C was observed on the syncytiotrophoblasts (STBs) and endothelial cells of placental villi. The immunoexpression of JAM-C was elevated in PE vs. normotensive (N) placentae. In the exchange villi, JAM-C immunoexpression was higher in the N+ve vs. N-ve group. However, in PE comorbid HIV infection, JAM-C expression was lower in the PE+ve vs. PE-ve group. Citrullinated histone-H3 concentration was lower in the N+ve vs. N-ve group but elevated in early-onset PE (EOPE)+ve vs. late-onset PE (LOPE)+ve group. These results indicate that PE and HIV-infected placentae individually express elevated JAM-C, manifesting in less neutrophil r-TM. However, in exchange villi of PE comorbid with HIV infection reduced JAM-C enhances neutrophil r-TM, thus supporting the synergistic effect of PE comorbid with HIV.
Endoscopic submucosal dissection versus endoscopic mucosal resection for the treatment of rectal lesions involving the dentate line
Authors: Kouladouros Konstantinos , Jakobs Johanna , Stathopoulos Petros , Kähler Georg , Belle Sebastian , Denzer Ulrike
Published: June 2024

Background

The ideal treatment of epithelial neoplastic rectal lesions involving the dentate line is a controversial issue. Piecemeal endoscopic mucosal resection (EMR) is the most commonly used resection technique, but it is associated with high recurrence rates. Endoscopic submucosal dissection (ESD) has been shown to be safe and effective for the treatment of rectal lesions, but evidence is lacking concerning its application close to the dentate line. The aim of our study is to compare ESD and EMR for the treatment of epithelial rectal lesions involving the dentate line.

Methods

We identified all cases of endoscopic resections of rectal lesions involving the dentate line performed in two German high-volume centers between 2010 and 2022. Periinterventional and follow-up data were collected and retrospectively analyzed.

Results

We identified 68 ESDs and 62 EMRs meeting our inclusion criteria. ESD showed a significant advantage in en bloc resection rates (89.7% vs. 9.7%; P = 0.001) and complete resection rates (72.1% vs. 9.7%; P = 0.001). The overall curative resection rate was similar between both groups (ESD: 92.6%, EMR: 83.9%; P = 0.324), whereas in the subgroup of low-risk adenocarcinomas ESD was curative in 100% of the cases vs. 14% in the EMR group (P = 0.002). There was one local recurrence after ESD (1,5%) vs. 16 (25.8%) after EMR (P < 0.0001), and the EMR patients required an average of three further interventions.

Conclusion

ESD is superior to EMR for the treatment of epithelial rectal lesions involving the dentate line and should be considered the treatment of choice.
Prevalence of weakness and factors mediating discrepancy between reported and observed leg weakness in people with sciatica
Authors: Dove Lucy , Baskozos Georgios , Kelly Thomas , Buchanan Elaine , Schmid Annina B.
Published: June 2024

Purpose

To establish the prevalence and agreement between reported and observed leg weakness in people with sciatica. To establish which factors mediate any identified difference between reported and observed leg weakness in people with sciatica.

Methods

68 people with a clinical diagnosis of sciatica, records from spinal service, secondary care NHS Hospital, England, UK reviewed. Primary outcome measures were the sciatica bothersome index for reported leg weakness and the Medical Research Council scale for observed weakness. Agreement was established with Cohen’s Kappa and intraclass correlation coefficient. Potential factors that may mediate a difference between reported and observed weakness included leg pain, sciatica bothersome index sensory subscale, age, hospital anxiety and depression subscale for anxiety.

Results

85% of patients reported weakness but only 34% had observed weakness. Cohen’s Kappa (0.066, 95% CI − 0.53, 0.186; p = 0.317)] and ICC 0.213 (95% CI − 0.26, 0.428, p = 0.040) both showed poor agreement between reported and observed weakness. The difference between reported and observed measures of weakness was mediated by the severity of leg pain (b = 0.281, p = 0.024) and age (b = 0.253, p = 0.042).

Conclusion

There is a high prevalence of reported leg weakness in people with sciatica, which is not reflected in observed clinical measures of weakness. Differences between reported and observed weakness may be driven by the severity of leg pain and age. Further work needs to establish whether other objective measures can detect patient reported weakness.
A fix and optimize method based approximate dynamic programming approach for the strategic fleet sizing and delivery planning problem
Authors: Aghazadeh Duygu , Ertogral Kadir
Published: June 2024

Logistics related costs constitute a major part in total cost of a product in general. Considering a company that delivers goods to its customers using its owned fleet, fleet ownership and operational costs together with the inventory costs compose the total logistics costs. In this study, we suggest an approximate Dynamic Programming algorithm, with a look ahead strategy, that uses the fix and optimize method as the imbedded heuristic for solving integrated fleet composition and replenishment planning problem. The total annual distribution cost factors considered in the problem are vehicle ownership costs, approximate routing costs, and inventory related costs. In this problem, we aim to minimize the total logistic cost by optimizing the fleet composition, replenishment patterns, and customers assigned to each vehicle in the fleet. We produced a set of reasonably large instances randomly and showed the efficacy of the suggested solution method.
Fear of failure and academic satisfaction: the mediating role of emotion regulation difficulties and procrastination
Authors: Duru Erdinç , Balkis Murat , Duru Sibel
Published: June 2024

This study investigates the mediating mechanisms that play a crucial role in the relationship between fear of failure and academic satisfaction and between fear of failure and procrastination. The study sample consists of 292 undergraduate students enrolled in different departments of the university. Within the scope of this study, emotion regulation difficulties may be one of the mediating mechanisms in this reciprocal relationship, the findings provide evidence that procrastination functions as a mediating variable in the relationship between fear of failure, difficulty in emotion regulation, and academic satisfaction while difficulty in emotion regulation acts as a mediator in the relationship between fear of failure and procrastination. Therefore, the findings of this study suggest that interventions aimed at improving the individual's emotion regulation skills may play an important role in overcoming the negative effects associate with the fear of failure on procrastination and academic satisfaction.
Invariant manifolds near $$L_1$$ and $$L_2$$ in the Sun–Jupiter elliptic restricted three-body problem I
Authors: Duarte Gladston , Jorba Àngel
Published: June 2024

In this paper, we present a way of combining the computation of invariant tori and their stable and unstable manifolds with the multiple shooting technique. We start by showing some of the results of Jorba (Nonlinearity 14(5):943–976, 2001) that should be modified in order to introduce the multiple shooting technique in these computations. After that, by a direct application in the planar elliptic restricted three-body problem (PERTBP), how to modify the equations and methods to compute the above-mentioned objects is introduced. In particular, the structure of the (systems of) equations and matrices involved in these computations is shown. An application of these computations can be found in Duarte and Jorba (Invariant manifolds of tori near $${L}_1$$

L
1

and $${L}_2$$

L
2

in the planar elliptic restricted three-body problem II. The Dynamics of Comet Oterma, Preprint 2023), where the dynamics of comet 39P/Oterma is modelled as a PERTBP.
The impact of measured income uncertainty on Spanish household consumption at the end of the Great Recession
Authors: Lugilde Alba
Published: June 2024

The aim of this paper is to study empirically the existence of precautionary saving in Spain at the end of the Great Recession using the micro data provided by the Spanish Survey of Household Finances. Using the panel component of these data, I construct a measure of income uncertainty for each household from the observed household real income and use it to test for the strength of precautionary saving. I find that an increase of 1% in the standard deviation of income reduces household consumption by 8.8% when using the logarithm of the household consumption as dependent variable; however, when using the ratio between consumption and average income as dependent variable, given the average normal income and consumption in the sample, consumption will decrease by 8.1%.
Graph realization of sets of integers
Authors: Wawrzyniak Piotr , Formanowicz Piotr
Published: June 2024

Graph theory is used in many areas of chemical sciences, especially in molecular chemistry. It is particularly useful in the structural analysis of chemical compounds and in modeling chemical reactions. One of its applications concerns determining the structural formula of a chemical compound. This can be modeled as a variant of the well-known graph realization problem. In the classical version of the problem, a sequence of natural numbers is given, and the question is whether there exists a graph in which the vertices have degrees equal to the given numbers. In the variant considered in this paper, instead of a sequence of natural numbers, a sequence of sets of natural numbers is given, and the question is whether there exists a multigraph such that each of its vertices has a degree equal to a number from one of the sets. This variant of the graph realization problem matches the nature of the problem of determining the structural formula of a chemical compound better than other variants considered in the literature. We propose a polynomial time exact algorithm solving this variant of the problem.
Seismo-stratigraphic and morpho-bathymetric analysis revealing recent fluid-rising phenomena on the Adventure Plateau (northwestern Sicily Channel)
Authors: Maiorana Mariagiada , Spatola Daniele , Todaro Simona , Caldareri Francesco , Parente Fabrizio , Severini Alessandro , Sulli Attilio
Published: June 2024

The northwestern region of the Sicily Channel hosts a great number of morphological highs, the widest of which is the Adventure Plateau that is part of the Sicilian Maghrebian Fold and Thrust Belt system, formed since the Neogene. The Adventure Plateau was shaped in the Early Pliocene by an extensional phase that produced high-angle normal faults mostly WNW-ESE to N-S oriented. Through these faults, magmatic fluids ascended and produced widespread volcanic manifestations often associated to fluid flow processes. The interpretation of multibeam echosounder, seismic reflection (sparker, airgun) and well-log data allow us to identify several features related to the presence of fluids in the study area. The morpho-structural analysis showed a NW–SE oriented fault system and a string of pockmarks that follow the same trend. A detailed well-log analysis confirmed the presence of oil traces, at a depth of ~ 250 m, and gas (i.e., CO2) at a depth of ~ 450 m. The seismo-stratigraphic analysis highlighted seismic signals located below the pockmarks, (e.g. seismic chimneys, bright spots) which suggest the presence of fluids that would rise to a few meters’ depth. Based on the observations, two sources and two corresponding rising mechanisms have been identified. Morphometric analysis of pockmarks has been performed to delineate their possible interaction with the bottom currents. A fluids pathway model has been reconstructed, revealing the source of fluids emissions at depth in the Adventure Plateau, and providing new insights into the identification of fluid leakage pathways.
Experimental bifurcation analysis of a clamped beam with designed mechanical nonlinearity
Authors: Hayashi Seigan , Gutschmidt Stefanie , Murray Rua , Krauskopf Bernd
Published: June 2024

We use control-based continuation (CBC) to perform an experimental bifurcation study of a periodically forced dual-beam. The nonlinearity is of geometric nature, provided by a thin, clamped beam. The overall system exhibits hysteresis and bistability in its open-loop frequency response due to a hardening, Duffing-like nonlinear stiffness, which can be designed or adjusted by choosing the properties of the thin beam. We employ local stabilising feedback control to implement CBC and track stable periodic solutions past the fold points. Thus obtained continuous solution branches are used to generate the solution surface over the plane of excitation amplitude and frequency. This surface features two curves of fold bifurcations that meet at a cusp point, and they delimit the experimentally observed bistability range of this nonlinear beam.
Students’ Holistic Reading of Socio-Scientific Texts on Climate Change in a ChatGPT Scenario
Authors: Cheung Kason Ka Ching , Pun Jack K. H. , Li Wangyin
Published: June 2024

ChatGPT becomes a prominent tool for students’ learning of science when students read its scientific texts. Students read to learn about climate change misinformation using ChatGPT, while they develop critical awareness of the content, linguistic features as well as nature of AI and science to comprehend these texts. In this exploratory study, we investigated students’ reading performance in comprehending two ChatGPT-generated socio-scientific texts, with one focusing on cognitive-epistemic aspects of climate science and another one focusing on social-institutional aspects of climate science. We theorized such reading of ChatGPT-generated outputs as encompassing the content-interpretation, genre-reasoning and epistemic-evaluation domains. Combining Rasch partial-credit model and qualitative analysis, we explored and investigated how a total of 117 junior secondary students (grades 8 to 9) read such texts. Moreover, we also examined how 55 students’ holistic reading of socio-scientific texts on climate change in a ChatGPT scenario changes after a reading-science intervention. Our findings indicate that the content-interpretation was the easiest while the epistemic-evaluation domains were the most difficult. Interestingly, after the reading-science intervention, many students developed their tentative view on nature of science when they evaluated ChatGPT’s claims; while a small increase in number of students discussed reliability and non-epistemic nature of AI when they evaluated ChatGPT’s claims in relation to climate change. The findings also drive a pedagogical model that improves students’ holistic reading of socio-scientific texts generated by ChatGPT.
Einschlafen mit einem Computerspiel?
Authors: Schlarb Angelika A. , Landwehr Janna , Schneider Barbara , Prehn-Kristensen Alexander , Quante Mirja
Published: June 2024

Hintergrund

Mittlerweile gibt es eine zunehmende Anzahl an Apps und digitalen Spielen mit dem mehr oder weniger expliziten Ziel der Gesundheitsförderung. Eines der häufig gesuchten Themen für Health-Apps ist Schlaf. Diese werden meist im Rahmen des abendlichen Zu-Bett-Geh-Rituals oder als Einschlafhilfe eingesetzt. Die Bewertung solcher Apps oder Spiele aus schlafspezifischer Perspektive wurde bislang jedoch wenig berücksichtigt. Daher hat diese Arbeit zum Ziel, einen Kriterienkatalog zur Bewertung für Expert*innen zu entwickeln und diesen in einer ersten Testphase zu erproben.

Methode

Mittels einer umfangreichen Literaturrecherche zum Thema Game-Kriterien sowie unter Hinzunahme ähnlicher Vorarbeiten wurde in einem mehrstufigen Prozess mit einem interdisziplinären Expertenteam ein Kriterienkatalog mit Fokus auf schlaf- und entspannungsbezogene Aspekte entwickelt. Dieser wurde in einer Pilotphase getestet.

Ergebnisse

Es zeigte sich, dass für „serious games“ bestehende Kriterienvorschläge zwar einige relevante Themenbereiche abdecken, diese jedoch bei einer Anwendung zur Schlafförderung durch ihre Ausrichtung aversive Effekte erwarten lassen. Neben einer zwingend erforderlichen Adaptation der Kriterien auf die Thematik Einschlafen bzw. Entspannung sind diese zudem um weitere Kriterien für Apps der Gesundheitsförderung zu erweitern. Diese Änderungen bzw. Adaptationen sind in der vorliegenden Arbeit erfolgt.

In der Pilotphase zeigten sich die vom interdisziplinären Team entwickelten Kriterien als weitestgehend sinnvoll und adäquat für die Thematik Schlaf bzw. Entspannung.

Diskussion

Neue Apps und Games hinsichtlich der Thematik Schlaf sollten unreflektiert weder genutzt noch von Fachpersonen empfohlen werden. Bereits bei der Erstellung einer solchen Anwendung ist dringend der Einbezug eines interdisziplinären Teams anzuraten. Der erarbeitete Kriterienkatalog kann in Zukunft Fachpersonal dabei unterstützen, schlaf- oder entspannungsbezogene Apps und Spiele zu bewerten und einzuordnen.
Metastatic Castration-Resistant Prostate Cancer: Advances in Treatment and Symptom Management
Authors: Kulasegaran Tivya , Oliveira Niara
Published: June 2024

Opinion statement

The management of metastatic castrate-resistant prostate cancer (mCRPC) has evolved in the past decade due to substantial advances in understanding the genomic landscape and biology underpinning this form of prostate cancer. The implementation of various therapeutic agents has improved overall survival but despite the promising advances in therapeutic options, mCRPC remains incurable. The focus of treatment should be not only to improve survival but also to preserve the patient’s quality of life (QoL) and ameliorate cancer-related symptoms such as pain. The choice and sequence of therapy for mCRPC patients are complex and influenced by various factors, such as side effects, disease burden, treatment history, comorbidities, patient preference and, more recently, the presence of actionable genomic alterations or biomarkers. Docetaxel is the first-line treatment for chemo-naïve patients with good performance status and those who have yet to progress on docetaxel in the castration-sensitive setting. Novel androgen agents (NHAs), such as abiraterone and enzalutamide, are effective treatment options that are utilized as second-line options. These medications can be considered upfront in frail patients or patients who are NHA naïve. Current guidelines recommend genetic testing in mCRPC for mutations in DNA repair deficiency genes to inform treatment decisions, as for example in breast cancer gene mutation testing. Other potential biomarkers being investigated include phosphatase and tensin homologues and homologous recombination repair genes. Despite a growing number of studies incorporating biomarkers in their trial designs, to date, only olaparib in the PROFOUND study and lutetium-177 in the VISION trial have improved survival. This is an unmet need, and future trials should focus on biomarker-guided treatment strategies. The advent of novel noncytotoxic agents has enhanced targeted drug delivery and improved treatment responses with favourable toxicity profiling. Trials should continue to incorporate and report health-related QoL scores and functional assessments into their trial designs.
A Note on Alexandrov Immersed Mean Curvature Flow
Authors: Lambert Ben , Mäder-Baumdicker Elena
Published: June 2024

We demonstrate that the property of being Alexandrov immersed is preserved along mean curvature flow. Furthermore, we demonstrate that mean curvature flow techniques for mean convex embedded flows such as noncollapsing and gradient estimates also hold in this setting. We also indicate the necessary modifications to the work of Brendle–Huisken to allow for mean curvature flow with surgery in the Alexandrov immersed, 2-dimensional setting.
Agent based modeling for intraday electricity markets
Authors: Alberizzi Andrea , Di Barba Paolo , Ziel Florian
Published: June 2024

In recent years, the strong growth of renewable energy sources has led to considerable instability in the electricity markets. As a consequence, this has increased trading activities in the continuous intraday market, especially close to delivery. This work presents an agent-based model that is able to reproduce the continuous market evolution, distinguishing players in dispatchable and non-dispatchable power plants and analyzing the behavior and interactions between them. All players behave rationally, trying to maximize their revenues and minimize imbalances. The results show that the model is able to reproduce the main characteristics of the continuous intraday electricity market, such as the price path strongly dependent on internal and external information, such as the wind production forecast, possible outages, an increase in order arrival towards the end of the trading session and weak market efficiency. The strategies assigned to each agent have been formulated taking into account statistical analyses of historical orders placed during continuous trading in different European bidding zones. The analyses have been carried out in a scenario composed of thermal plants with different marginal costs and wind agents, but the flexibility of the model gives the possibility to study many different scenarios.
A Systematic Review of Personal Information Sharing in Smart Cities: Risks, Impacts, and Controls
Authors: Alabsi Maha Ibrahim , Gill Asif Qumar
Published: June 2024

Smart cities aim to deliver smart services that rely on emerging technologies to their users. In order for users to get the provided services, they need to share their personal information with different parties. However, sharing personal information in smart cities may impact the privacy of that information. Thus, there is a need to address privacy risks relevant to sharing personal information in smart cities. This study aims to address this issue by conducting a systematic literature review (SLR) to identify and extract privacy risks, impacts, and existing controls associated with sharing personal information, considering elements involved and interacting during the sharing activity in smart cities. A set of 83 selected studies in both academic and industry fields were reviewed, and the results were categorised into three main groups: privacy risks, impacts, and controls. Moreover, the implications and future research directions were also reported. The proposed privacy risk taxonomy will provide a much-needed foundation for the industry and research community, intending to research and evaluate privacy risk frameworks and design solutions for sharing personal information in smart cities.
Early stage thymoma and the surgical extent paradigm
Authors: Kocaman Gökhan , Kayi Cangir Ayten
Published: June 2024

The recommended treatment for early stage thymoma without myasthenia gravis is complete thymectomy (CT). Limited thymectomy (LT) (simply resecting the thymoma with safe surgical margins) is gaining popularity. In this study, we compared the surgical and oncological results of complete and limited thymectomy in non-myasthenic patients with early stage thymoma. Non-myasthenic, Masaoka stage I–II, 86 patients who underwent surgical resection for thymoma were included in the study. Complete thymectomy (n:44) included patients who had resection of the thymoma together with the entire thymus and limited thymectomy (n:42) included patients who had resection of the thymoma without remaining thymus. The surgical approach, tumor size, histological type, pathological stage, adjuvant therapy, complications, postop myasthenia gravis, recurrence and death were recorded and compared between groups. Complete thymectomy group had more WHO type B1-3 tumors, more complications and more deaths than patients in the limited thymectomy group (p = 0.03, 0.018 and 0.023 respectively). Although statistically not significant CT group had more recurrences than LT group (11.4%/4.8%, p = 0.43). The 10-year freedom from recurrence (FFR) rate in the CT group was 84.8% and in the LT group ıt was 97.6%, the difference was not statistically significant (p = 0.15). None of the factors including surgical extent analysed with univariate and multivariate analysis had a significant effect on FFR. Limited thymectomy may be a good treatment option for non-myasthenic early stage thymoma patients but randomized controlled trials with long follow-up periods, ideally comparing patients operated with minimally invasive surgery are necessary.
SARS-CoV-2 Resistance to Small Molecule Inhibitors
Authors: Lopez Uxua Modrego , Hasan Md. Mehedi , Havranek Brandon , Islam Shahidul M.
Published: June 2024

Purpose of the Review

SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.

Recent Findings

Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.

This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.
Screening of hypercortisolism among patients with hypertension: an Italian nationwide survey
Authors: Di Dalmazi G. , Goi J. , Burrello J. , Tucci L. , Cicero A. F. G. , Mancusi C. , Coletti Moia E. , Iaccarino G. , Borghi C. , Muiesan M. L. , Ferri C. , Mulatero P.
Published: June 2024

Purpose

Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy.

Methods

A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vs non-excellence), geographical area, and medical specialty.

Results

Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres.

Conclusions

Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived.
Serum alkaline phosphatase is a strong predictor of mortality in ESKD patients: analysis of the RISCAVID cohort
Authors: Panichi Vincenzo , Rosati Alberto , Mangione Emanuela Antonella , Incognito Federica , Mattei Silvia , Cupisti Adamasco
Published: June 2024

Background

Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis techniques. This study aimed to assess the role of alkaline phosphatase serum levels on cardiovascular and overall mortality in the RISCAVID study cohort through a long follow-up period, looking for associations with known risk factors for poor outcome.

Methods

In June 2004, a prospective observational study was started focusing on the cardiovascular risk in hemodialysis patients who lived in the north-west area of Tuscany (RISCAVID, “RISchio CArdiovascolare nei pazienti afferenti all’Area Vasta In Dialisi”). The RISCAVID cohort included 572 prevalent patients on maintenance HD for at least three months. Morbid or fatal events were prospectively recorded at 6-month intervals for a follow up time of 216 months.

Results

In univariable Cox regression analysis, dialysis technique, Geriatric Nutritional Risk Index, peripheral vascular disease, and intact parathyroid hormone and total calcium serum levels were significantly associated with baseline alkaline phosphatase serum levels. Cox multivariable analysis showed that elevated serum alkaline phosphatase levels (the highest quartile), advanced age, dialysis vintage, type of vascular access, Geriatric Nutritional Risk Index, C-reactive protein and calcium serum levels, history of cardiovascular disease and peripheral vascular disease were independent predictors of overall mortality in maintenance HD patients. The fourth quartile of alkaline phosphatase was associated with all-cause 10-year mortality (HR: 1.47; 95% CI: 1.177–1.834) with a 47% increase with respect to the 1st, 2nd, and 3rd quartiles. This was also observed for 18-year all-cause mortality.

Conclusions

Adjusted proportional analysis showed the alkaline phosphatase value to be an independent and powerful predictor of overall mortality in the hemodialysis population.

Graphical Abstract
Situating Cognitive Science after 1945
Authors: Ash Mitchell G.
Published: June 2024

The paper attempts to place the emergence of cognitive science (CS) as an interdisciplinary research program in historical context. A broad overview of the institutional and intellectual situations during the early postwar period is presented, focusing primarily on psychology and artificial intelligence (AI). From an institutional perspective, the paper shows that although computers and computer science were closely linked with weapons research during World War II, the postwar creation of cognitive science had no military connection, but was largely enabled by small grants from private foundations, though the RAND Corporation was involved to a limited extent. From an epistemic perspective, the paper shows: (1) that neobehaviourist learning theory was not replaced by, but flourished parallel to cognition-oriented psychology in the 1950s, because they were located in different sub-disciplines; (2) that the key theoretical inputs into CS were developed separately at first, and each group remained affiliated with the discipline or complex of disciplines from which it came. A certain tension remained at the core of the project between the machine dreams of the emerging AI community and the idea of autonomous mental processes central to cognitive psychology.
New belief divergence measure based on cosine function in evidence theory and application to multisource information fusion
Authors: Liu Xiaoyang , Xie Cheng , Liu Zhe , Zhu Sijia
Published: June 2024

Multisource information fusion technology significantly benefits from using information across various sources for decision-making, particularly by leveraging evidence theory to manage uncertain information efficiently. Nonetheless, dealing with highly conflicting evidence presents a considerable challenge. To tackle this issue, this paper introduces a new belief divergence measure within the framework of evidence theory. The proposed measure, which incorporates the cosine function and pignistic probability transformation, is adept at quantifying the disparity between the evidences while maintaining key properties, such as boundedness, non-degeneracy and symmetry. Moreover, building upon the concepts of proposed belief divergence and belief entropy, this paper further proposes a new fusion method that employs a weighted evidence average prior to the application of Dempster’s rule. The performance of the proposed method is validated on several applications, and the results demonstrate its superior ability to absorb highly conflicting evidence compared with existing methods.
The Effects of Sterilisation on Abiotic Soil Properties and the Challenge this Poses to Untangling the Influence of Abiotic and Biotic Soil Variables on Plant Growth
Authors: Manea Anthony , Leishman Michelle R. , Geraghty Dylan M. , Perera Sashini D. , O’Hare Jessica A. , Gil-Fernández Margarita , Tabassum Samiya , Le Roux Johannes J.
Published: June 2024

To separate the effects of the abiotic and biotic soil components on plant growth, researchers can compare plants grown in sterilised and unsterilised soil (unsterilised soil approach). However, using this approach can be problematic if the abiotic component of the soil is affected by the sterilisation treatment, which is often the case. We aimed to determine how often this approach is used by plant-soil interaction studies and demonstrate how it can impact plant growth. We reviewed the relevant literature to determine how often the unsterilised soil approach is used and whether the studies that use it acknowledge the ‘soil sterilisation’ caveat. We then conducted a glasshouse experiment to demonstrate the effect that soil sterilisation has on selected soil nutrients and consequently on plant growth. Our literature review revealed that of the studies that used the unsterilised soil approach, only 23% measured and reported soil nitrogen or phosphorus before and after sterilisation, with 50% of these reporting a change in one or both nutrients. We then showed that the growth of our study species, Eucalyptus saligna, was greater when grown in sterilised soils compared to unsterilised soils. Interestingly, there was a strong positive relationship between the change in ammonium nitrogen and E. saligna growth between the sterilised and unsterilised soils. Given our findings, we advocate that studies that use the unsterilised soil approach should measure the abiotic soil properties before and after sterilisation and if differences are found, these studies should use the inoculation approach instead.
Multi-agent Gradient-Based Off-Policy Actor-Critic Algorithm for Distributed Reinforcement Learning
Authors: Ren Jineng
Published: June 2024

This paper proposes a gradient-based multi-agent actor-critic algorithm for off-policy reinforcement learning using importance sampling. Our algorithm is incremental with full gradients, and its complexity per iteration scales linearly with the size of approximation features. Previous multi-agent actor-critic algorithms are limited to the on-policy setting or off-policy emphatic temporal difference (TD) learning and they do not take advantage of the advances in off-policy gradient temporal difference learning (GTD). As a theoretical contribution, we establish that the critic step of the proposed algorithm converges to the TD solution of the projected Bellman equation and the actor step converges to the set of asymptotically stable fixed points. Numerical experiments on the multi-agent generalization of the Boyan’s chain problem show that the proposed approach provides improved performances in terms of stability and convergence rate as compared with the state-of-the-art baseline algorithm.
Proton Pump Inhibitor for Gastrointestinal Bleeding in Patients with Myocardial Infarction on Dual-Antiplatelet Therapy: A Nationwide Cohort Study
Authors: Baik Minyoul , Jeon Jimin , Kim Jinkwon , Yoo Joonsang
Published: June 2024

Background

Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT.

Methods

This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk.

Results

Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47–0.70; P < 0.001). The benefits of PPIs were consistent in high-risk (HR, 0.71; 95% CI, 0.45–1.13; P = 0.147) and low-risk (HR, 0.54; 95% CI, 0.43–0.68; P < 0.001) patients (P for interaction = 0.481).

Conclusions

Among Korean patients with MI receiving DAPT, PPIs were underutilized, even among those at high risk of severe UGI bleeding. Nonetheless, PPI use reduced severe UGI bleeding in low- and high-risk groups.
Application of system dynamics to evaluate reduction targets for the entry of solid waste into a landfill site
Authors: Ibargüen Rodríguez Sandra Lorena , Flores Cuautle Jose de Jesus Agustin
Published: June 2024

The waste produced around the world increases daily due to population increase and the fact that life expectancy is longer. Waste production is higher in urban environments; therefore, managing Urban Solid Waste must be more rigorous to avoid environmental problems and health effects. For this reason, standards are created to properly manage landfills so that each life cycle stage is managed responsibly. However, a solid commitment from the community and more management regulations from the government are needed to be focused on reducing, reusing, and recycling materials as much as possible. This commitment needs to be reinforced to the extent that regulatory policies are created at the household level as much as education and awareness programs are implemented. This study presents a method to evaluate how imposing waste management goals before they reach landfills can increase the lifetime of landfills and, consequently the suitableness of a treatment plant implementation.
Siting Considerations for Satellite Observation of River Discharge
Authors: Eggleston Jack , Mason Chris , Bjerklie Dave , Durand Mike , Dudley Rob , Harlan Merritt
Published: June 2024

With growing global capability for satellite measurement of river discharge (flow) comes a need to understand and reduce error in satellite‐based discharge measurements. Satellite‐based discharge estimates are based on measurements of water surface width, elevation, slope, and potentially velocity. Site selection is important for reducing error and uncertainty in both conventional and satellite‐based discharge measurements because geomorphic river characteristics have strong control over the relationships between discharge and width, water surface elevation (or depth), slope, and velocity. A large ground‐truth data set of 8,445 conventional hydraulic measurements, collected by acoustic Doppler current profilers at 503 stations in the United States, was developed and quality assured to examine correlation between river discharge and water surface width, depth, velocity, and cross‐sectional area. A separate database of river surface slope and discharge time‐series was developed from paired continuous monitoring stations to examine slope‐discharge correlations. Results show that discharge correlates most strongly with velocity, cross‐sectional area, depth, width, and slope, in that order. Uncertainty of satellite discharge estimates is affected by observed hydraulic variable and reach‐specific variability in observed variable(s) characteristics including range of variability, georegistration accuracy, and stability over time of relationships between discharge and observed hydraulic variable.
N6-methyladenosine modified TGFB2 triggers lipid metabolism reprogramming to confer pancreatic ductal adenocarcinoma gemcitabine resistance
Authors: Ma Ming-Jian , Shi Yin-Hao , Liu Zhi-De , Zhu Ying-Qin , Zhao Guang-Yin , Ye Jing-Yuan , Li Fu-Xi , Huang Xi-Tai , Wang Xi-Yu , Wang Jie-Qin , Xu Qiong-Cong , Yin Xiao-Yu
Published: June 2024

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.
Postnatal corticosteroid therapy in bronchopulmonary dysplasia - why animal studies disagree with clinical trials?
Authors: Harijith Anantha , Raffay Thomas M. , Ryan Rita M.
Published: June 2024

The systematic review and meta-analysis of newborn animal models by Irene Lok et al. is the first to extensively summarize the literature regarding postnatal systemic corticosteroid use on lung development of newborn rodent models. The meta-analysis showed that the use of postnatal corticosteroids resulted in a reduction in body weight along with persistent alveolar simplification. The most frequently used corticosteroid was dexamethasone. Corticosteroids have been extensively used in clinical trials in preterm newborns. Trials using early systemic administration of corticosteroids reduced the rate of BPD or mortality with no increase in the rates of cerebral palsy. Use of late systemic corticosteroids (administered >7 days after birth) also reduced the rate of BPD, mortality, and combined outcome of mortality or BPD. Late systemic corticosteroids showed no impact on the rates of neurodevelopmental outcomes in later childhood. It is important to note that later stages of inflammation leading to a more severe form of BPD continues to be a problem with no clear therapy in sight. The authors made a critical point in their paper – the negative effects of steroids were greater in the normal lung control animals than in the injured. This conveys caution in using steroids in a prophylactic manner.

Impact

Use of systemic corticosteroids in clinical trials have shown good response in preterm neonates evidenced by reduced rate of bronchopulmonary dysplasia.

Rodent models have not shown a similar beneficial response.

Use of systemic corticosteroids have caused greater arrest of lung development in rodent models with normal lungs compared to those with lung damage.
FGF signaling modulates mechanotransduction/WNT signaling in progenitors during tooth root development
Authors: Pei Fei , Guo Tingwei , Zhang Mingyi , Ma Li , Jing Junjun , Feng Jifan , Ho Thach-Vu , Wen Quan , Chai Yang
Published: June 2024

Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis. Here, we used tooth root development as a model to explore the roles of FGF signaling and mechanotransduction as well as their interaction in regulating the progenitor cell fate decision. We show that Fgfr1 is expressed in the mesenchymal progenitor cells and their progeny during tooth root development. Loss of Fgfr1 in Gli1+ progenitors leads to hyperproliferation and differentiation, which causes narrowed periodontal ligament (PDL) space with abnormal cementum/bone formation leading to ankylosis. We further show that aberrant activation of WNT signaling and mechanosensitive channel Piezo2 occurs after loss of FGF signaling in Gli1-CreER;Fgfr1fl/fl mice. Overexpression of Piezo2 leads to increased osteoblastic differentiation and decreased Piezo2 leads to downregulation of WNT signaling. Mechanistically, an FGF/PIEZO2/WNT signaling cascade plays a crucial role in modulating the fate of progenitors during root morphogenesis. Downregulation of WNT signaling rescues tooth ankylosis in Fgfr1 mutant mice. Collectively, our findings uncover the mechanism by which FGF signaling regulates the fate decisions of stem/progenitor cells, and the interactions among signaling pathways and mechanotransduction during tooth root development, providing insights for future tooth root regeneration.
Evidence for the formation of silicic lava by pyroclast sintering
Authors: Foster Annabelle , Wadsworth Fabian B. , Tuffen Hugh , Unwin Holly E. , Humphreys Madeleine C. S.
Published: June 2024

Silicic lavas can be produced by the sintering of pyroclasts in the volcanic sub-surface, and then advected out of the vent. Here, we provide evidence for this mechanism preserved in the exposed post-glacial remnants of a silicic volcanic conduit at Hrafntinnuhryggur, Krafla volcano, Iceland. We show that the conduit margins are a clast-supported pumice lapilli tuff deposit that grades continuously into dense obsidian and that the obsidian contains cuspate relict clast boundaries and country rock lithic fragments throughout. Transects of H2O concentrations across the conduit show that the magma was degassed to different degrees laterally with systematic spatial variation that is consistent with progressive conduit clogging and final gas pressurisation. Textures in the overlying effusive lavas record the variably sheared and brecciated remnant of the same in-conduit sintering. This record of a silicic conduit system connected to upper eruptive deposits provides support for the ‘cryptic fragmentation model’ for effusive silicic volcanism.