bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative online international learning as a third space to improve students’ awareness of cybersecurity
Authors: Lui Alison , Womack Catharina , Orton Penny
Published: January 2025

This article critically evaluates the effects of the ACU Virtual Mobility (VM) Project Digital Information Security Course (DISC) programme on improving students’ awareness of cyber security skills, pre and post the educational intervention. Our selected VM tool is Collaborative Online International Learning (COIL). Building on a conceptual framework of COIL as a Third Space for teaching students from different countries, we show that COIL has a positive effect on glocalising cybersecurity. This enabled students to share their local experiences but work towards global solutions, since cybersecurity threats are global concerns. A cross-sectional survey design was used, with data collected using online questionnaires. The research was conducted at the Durban University of Technology (DUT), South Africa and at Liverpool John Moores University (LJMU), United Kingdom. Census sampling identified programme participants from DUT and LJMU, registered at the respective universities in 2024. Data were analysed statistically using descriptive statistics, Chi-square test of independence, One sample t-test and independent samples t-test. Results indicated that students reported cyber security as a high priority. This study confirms that students who are aware of cyber bullying have a greater ability to ensure their cyber security. An interesting finding was the difference between DUT and LJMU students on collaboration skills (M = 4.84, t=(48.301) 2.478, p = .017). The major contribution is the use of COIL as an educational intervention to increase students’ cyber security awareness and enrich their learning experiences. Educators should consider adopting COIL as a pedagogical tool to educate students on cybersecurity and AI. This project has policy impact on social mobility and educational policies of the UK. We provide evidence to the ongoing dialogue in South Africa regarding student mobility and a stronger emphasis on short-term virtual mobility exchanges. This study focused on students who participated in the ACU virtual mobility project, DISC; therefore, the results may not be generalised to other projects of a similar nature. This study does not consider the long-term effects of this intervention on increasing cyber security awareness because it was of a cross-sectional design.
Child Emotional Characteristics as Predictors of Informant Disagreement in Oppositional Defiant Symptomatology
Authors: González-Lorza Andrea , Navarro José-Blas , Ezpeleta Lourdes , Osa Nuria de la
Published: January 2025

The present study examines the disagreement between parents and teachers on the Oppositional Defiant Disorder Symptomatology (ODS) in children and how sociodemographic factors like gender and socio-economic status (SES); and emotional characteristics such as aggressiveness, temperament, callousness; anxious and depressive symptoms, and irritability may be predictors of this incongruence. A community sample of 614 3-year-old, followed up until age 14 (N = 287) was obtained from a longitudinal study that began in 2009. Parents and teachers completed an ODS scale and multiple questionnaires about child´s emotional difficulties. Analyses indicated that parent-teacher ratings were discrepant, and this disagreement diminished with age (Intraclass Correlation Coefficient = 0.12 to 0.69) with parents consistently reporting higher ODS scores compared to teachers across various ages. Predictors of parent-teacher disagreement on ODS were analyzed using polynomial regression with second and third order interactions. Results revealed that disagreement was higher when rating females, and for children belonging to low + low/medium or high SES groups. Lower ratings of aggressiveness, callousness and irritability, while higher scores of effortful control were significant predictors of higher parent-teacher ODS discrepancies. Research on how child affective variables influence multi-informant disagreement could lead to better clinical practice in addition to more accurate assessment and diagnosis in the infant-juvenile population.
Antimicrobial and Antibiofilm Activity of Analogous Synthetic Peptides from Anoplin, Temporin, and Aurein
Authors: Cruz Orozco Kevin , Ibarra Valencia Marco Antonio , Barrios Camacho Humberto , Corzo Burguete Gerardo , Arenas Sosa Iván
Published: January 2025

Introduction

The antibacterial, anti-biofilm, and hemolytic activities of five synthetic analogs of Anoplin, Temporin, and Aurein were evaluated.

Methods

Five peptides, varying in length from ten to thirteen amino acids, were chemically synthesized to preserve the physicochemical characteristics inherent to the original antimicrobial peptides. These characteristics included the hydrophobic ratio, Boman index, GRAVY, stability index, and aliphatic index, with the additional objective of enhancing their antimicrobial effectiveness.

Results

The most promising peptides were derived from Anoplin, particularly Anoplin_k1, which was identified as the most hydrophobic peptide with a net charge of + 2; however, it exhibited slightly increased hemolytic activity compared to the other four peptides. Anoplin_k1 demonstrated efficacy that was comparable to reference strains as well as against clinically isolated bacterial strains. The synthetic peptide Temporin ALk_k3, an analog of Temporin Alk, did not show antimicrobial activity above 100 µg/mL. Antibiofilm activity was evaluated against E. coli (K12), P. aeruginosa (PA01), and S. aureus (SH1000) reference strains.

Conclusions

The peptide demonstrating the most significant antibiofilm activity was Anoplin_k1 (≤ 64 µg/mL), whereas the Aurein derivatives exhibited reduced antibiofilm activity.
Interventions to Prevent Relapse or Recurrence of Preconception Anxiety and/or Depression in Perinatal Women: A Systematic Review
Authors: Rae Celia , McRae Rebecca , Holliday Elizabeth , Chojenta Catherine
Published: January 2025

Objectives

Women with preconception anxiety and/or depression experience high rates of relapse or recurrence of the disorders in the perinatal period. This review aimed to identify perinatal interventions that were designed to prevent relapse or recurrence in women with a history of anxiety and/or depression.

Methods

The review was conducted based on the PRISMA guidelines. Six medical databases were searched with specific search strategies for each. The reference lists of literature reviews retrieved in this search were also screened, as well as the reference lists of reviews identified within these reviews. Additionally, the publications of the first authors of included studies were reviewed for relevant articles.

Results

There were 10 articles eligible for inclusion. These articles described pharmacological or dietary supplement interventions, as well as psychological and/or behavioural interventions. All identified studies focused on the prevention of recurrent depression, comprising four antenatal interventions and six postnatal interventions. No studies reporting interventions for the prevention of recurrent anxiety were identified.

Conclusions for Practice

Several published studies provided evidence supporting the use of prophylactic antidepressants and progesterone to prevent relapse or recurrence of depression, although studies were limited by small sample sizes and the potential for study bias. More recent and higher quality evidence exists for the role of mindfulness and cognitive behavioural therapy in the prevention of depressive relapse. Further exploration of relapse prevention strategies for women with preconception anxiety and/or depression is required, particularly for recurrent anxiety.
Modern Micropolitics of Antipopulism: Rethinking Discourse and Empathy
Authors: Séville Astrid
Published: January 2025

In recent years, the debate on right-wing populism has led to numerous calls for the defense of liberal democracy, especially in Germany. The question of the extent to which liberal democracy depends on certain values, attitudes, and behavior has been raised from various sides. This article analyzes this public debate by focusing on publications that formulate recommendations for dealing with right-wing populists. These texts not only reflect on the possibilities and limits of rational debate between citizens but also promote an ideal of the good liberal democrat. The interventions can thus be understood as contemporary codes of conduct that contain elements of social and democratic theories and translate them into practical considerations. Ultimately, they represent a kind of self-undermining post-Habermasian discourse ethics.
LLMs, Truth, and Democracy: An Overview of Risks
Authors: Coeckelbergh Mark
Published: January 2025

While there are many public concerns about the impact of AI on truth and knowledge, especially when it comes to the widespread use of LLMs, there is not much systematic philosophical analysis of these problems and their political implications. This paper aims to assist this effort by providing an overview of some truth-related risks in which LLMs may play a role, including risks concerning hallucination and misinformation, epistemic agency and epistemic bubbles, bullshit and relativism, and epistemic anachronism and epistemic incest, and by offering arguments for why these problems are not only epistemic issues but also raise problems for democracy since they undermine its epistemic basis– especially if we assume democracy theories that go beyond minimalist views. I end with a short reflection on what can be done about these political-epistemic risks, pointing to education as one of the sites for change.
Determination of the Electric Field by Particle Tracking in a Plasma Sheath Region during Free Fall
Authors: Schmitz Andreas S. , Hanstein Luisa , Klein Max , Kretschmer Michael , Lotz Christoph , Shemakhin Aleksandr , Thoma Markus H.
Published: January 2025

In this work we present an experiment in which we injected microspheres at low pressure into a capacitively coupled argon plasma chamber. The setup was located in the top point of the Einstein-Elevator drop tower in Hannover, Germany, where the microparticles reached their equilibrium position above the lower electrode during

$$1 \, g$$

1

g

. During the fall, the trajectories of the microparticles, which were driven by the electric force, the neutral drag force and some residual gravitational force, were recorded. In addition, simulations of the plasma conditions were performed with commercial software to determine the microparticle charges via an orbital motion limit theory approach, taking into account the charge exchange in ion-neutral collisions. Based on the calculated position dependence of the microparticle charges and the electric force, the electric field present in the plasma sheath region was finally determined.
Beef, butter, and broth: cooking in 16th-century Sweden
Authors: Maltin Emma , Leino Matti Wiking , Rosén Christina , Isaksson Sven
Published: January 2025

We present the organic residue analysis of sherds of 50 cooking vessels from the 16th-century town of Nya Lödöse, Sweden. We confirm previous analyses showing that lipids are absorbed by glazed ceramic. By analyses of biomarkers and compound-specific stable carbon isotope analyses of fatty acids, we show that pipkins and pans were used for cooking ruminant carcass products, dairy, and plant foods. The dominance of ruminant fat and dairy reflects the importance of oxen and butter in the local food culture. The vessels included in the present study show some degree of specialized function. Pipkins had more traces of ruminant carcass fats compared to pans. Medium and large-sized pipkins contained a combination of animal fats and plant traces, possibly representing the preparation of stews. In contrast, the smallest pipkins showed no traces of plant foods and might have been used to melt animal fat. Pans had more traces of butter and had been exposed to higher temperatures, indicating frying. Flat pans were, to a higher degree, used for the frying of fish than the deep ones, but fish seem nonetheless to be underrepresented in the lipid residue data. According to zooarchaeological and historical data, fish, pork, and poultry were important parts of the diet, but as traces of these foodstuffs are scarce in the organic residue analysis, it may be inferred that they were prepared differently—boiled in metal cauldrons, roasted on metal spits over the open fire, or consumed in their dried, salted, or smoked state without further preparation.
Short-term outcomes of low anterior resection with and without ileostomy for low, mid and upper rectal cancers
Authors: Xu Vincent , La Kristina , Ma Rachel , Solis-Pazmino Paola , Smiley Abbas , Barnajian Moshe , Ellenhorn Joshua , Bergamaschi Roberto , Nasseri Yosef
Published: January 2025

Although the addition of an ileostomy to low anterior resection (LAR) may often be considered preventative of anastomotic leakage (AL), evidence that clearly demonstrates such benefit is lacking. This study aimed to identify the impact of adding an ileostomy upon AL and organ-space surgical site infection (SSI) rates in patients with lower, middle, or upper rectal cancer. This case–control study included rectal cancer patients who had undergone elective LAR in the American College of Surgeons-National Surgical Quality Improvement Program dataset between 2016 and 2022. Patients with lower, middle, and upper tumors were identified and analyzed according to whether an ileostomy was added or not. Patients’ pre-, intra-, and short-term post-operative data were compared using univariable and multivariable methods. A total of 4048 patients (61.6% males) with a mean age of 60 years, whereof 1166 with lower, 1836 with middle, and 1046 with upper tumors were identified. An ileostomy was added in 2804 (69.3%) patients. Patients with upper tumors had an ileostomy added less frequently (78.5%vs 74.5% vs 49.9%, p < 0.001). The overall AL and organ-space SSI rates were 4.3% and 6.7%. There were no statistically significant differences in AL and organ-space SSI rates (requiring or not requiring re-intervention or re-operation) between patients with and without ileostomy regardless of tumor location. Multivariable logistic regression controlling for confounding variables showed no association between adding an ileostomy and AL and organ-space SSI rates (requiring or not requiring re-intervention or re-operation) regardless of tumor location. This case–control study did not find any evidence in support of a preventative impact upon AL and organ-space SSI rates of adding an ileostomy to LAR in patients with lower, middle, or upper rectal cancer.
Roles of Prostaglandins and Cyclooxygenases in Autism Spectrum Disorder: A Comprehensive Review
Authors: Kamal Datu Agasi Mohd , Abidin Shahidee Zainal , Saudi Wan Salman Wan , Kumar Jaya , Bellato Alessio
Published: January 2025

Purpose of Review

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with multifaceted etiologies. Emerging evidence implicates dysregulation of prostaglandins and cyclooxygenase (COX) enzymes in ASD pathophysiology. This review aims to explore key mechanisms through which prostaglandins and COX enzymes may influence ASD.

Recent Findings

Recent research highlights significant roles for prostaglandins and COX enzymes in modulating Wnt (Wingless and Int-1) signalling pathways, which are known autism susceptibility pathways, as well as in regulating dendritic arborisation and cerebellar function. Polymorphisms in COX genes have also been linked to ASD, indicating a genetic component to this dysregulation. Furthermore, prostaglandins and COX enzymes show potential as biomarkers for ASD.

The accumulated evidence underscores the involvement of prostaglandins and COX enzymes in ASD pathophysiology. This insight offers a deeper understanding of the disorder and may pave the way for more effective diagnostic and treatment strategies.
Hepcidin peptide controls the inflammatory response induced by betanodavirus infection and improves European sea bass (Dicentrachus labrax) survival
Authors: Cervera Laura , Arizcun Marta , Mercado Luis , Cuesta Alberto , Chaves-Pozo Elena
Published: January 2025

Nervous necrosis virus (NNV) is the etiological agent of viral encephalopathy and retinopathy in many fish species, including European sea bass (Dicentrachus labrax) and is of great economic losses to fish farmers. To solve this problem in fish production, antimicrobial peptides (AMPs) have been identified as potential candidates for NNV treatment in aquaculture. Hepcidin (Hamp) is one of the most promising AMPs. Thus, we aimed to evaluate the therapeutic application of Hamp synthetic peptide after NNV challenge. Hamp was able to significantly increase survival rates and ameliorate clinical signs of the disease, though the viral levels, determined by viral replication and immunolocalization, were not affected. Synthetic Hamp increased the immunoglobulin M (IgM) and AMP protein levels in serum and some tissues respect to the levels found in NNV-infected fish. However, Hamp peptide decreased the NNV-induced bactericidal activity. At the gene level, Hamp exerted anti-inflammatory properties, reducing the pro-inflammatory response orchestrated by NNV, probably preventing neuronal damage. Apart from this, Hamp up-regulated the expression of adhesion molecules that facilitated the recruitment of immune cells, namely T helper and B cells, probably to orchestrate the adaptive response. To conclude, Hamp immunomodulatory properties and therapeutic application against NNV are very promising for its use in aquaculture.
Comparing haploidentical transplantation with post-transplantation cyclophosphamide and umbilical cord blood transplantation using targeted busulfan in children and adolescents with hematologic malignancies
Authors: Hong Kyung Taek , Kim Bo Kyung , An Hong Yul , Choi Jung Yoon , Song Sang Hoon , Yu Kyung-Sang , Jang In-Jin , Kang Hyoung Jin
Published: January 2025

Purpose

This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies.

Methods

Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed.

Results

The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05).

Conclusions

These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients without human leukocyte antigen-matched donors.
Copeptin Association with Theory of Mind, Cognitive Functions and Symptom Severity in Children with Autism Spectrum Disorder
Authors: Polónyiová Katarína , Babková Jaroslava , Babinská Katarína , Ostatníková Daniela
Published: January 2025

Arginine vasopressin (AVP) is a neuropeptide whose dysregulation has previously been associated with symptom severity in children with Autism spectrum disorder (ASD), theory of mind (ToM) deficits as well as problems with memory consolidation. However, AVP is rarely measured because of its short half-life and laborious method of detection. Copeptin is a more stable peptide derived from the same precursor molecule and considered a reliable surrogate marker of AVP. The goal of this study was to analyze copeptin levels in children with ASD and to investigate the relationships to their symptom severity, ToM and intellect. Our research sample consisted of 49 children with ASD, 40 boys and 9 girls, aged 6–12 years, in the IQ range of 70–132. Participants were diagnosed at the Academic Research Center for Autism at the Institute of Physiology on the Faculty of Medicine of Comenius University, using ADOS-2 and ADI-R. We used the comic strip task to measure ToM and Woodcock-Johnson International Editions II to assess cognitive abilities of participants. Plasma copeptin levels were evaluated by the ELISA method. Based on the results of Spearman’s correlation coefficient, we identified moderately strong correlations between copeptin concentrations and the restricted, repetitive, and stereotyped patterns of behavior, creativity, thinking ability, memory for names and to a ToM subscale Intentions, but not with overall ToM. Our findings provide evidence of relationships between plasmatic copeptin, a surrogate marker of AVP, and certain behavioral characteristics of children with ASD, in which the involvement of AVP has been assumed.
Strike-Slip Terrains and Transform Margins
Authors: Nemčok Michal , Doré Anthony G. , Henk Andreas , Doran Helen
Published: January 2025

Many of the world's continents are bounded or traversed by vast fault networks that move laterally, like the well-known San Andreas Fault. As well as being major tectonic features of the Earth's surface, these strike-slip regimes are vitally important to the world's natural resources – petroleum, water, and geothermal energy. This book covers all aspects of these regimes; how they initiate; how they develop; and the natural resources associated with them. Numerous global case studies illustrate structural development, thermal and fluid flow implications, and commercial applicability. No other book provides such a comprehensive overview of these settings, and this volume will stand as a critical reference of the state of knowledge of strike-slip terrains and transform margins. It will be invaluable for a broad range of readers, from advanced students of geology and researchers specializing in strike-slip regimes to geoscientists and managers involved in natural resources and energy solutions.
Principles of Finance
Authors: Bodie Zvi , Merton Robert C. , Thakor Richard T.
Published: January 2025

Written for the MBA or undergraduate first course in finance, as well as follow-on courses, this textbook provides a clear, accessible, and thorough explanation of the principles of finance; how they connect to real-world practice and how they are used to solve problems. Structured around ten unifying principles representing the core tenets of the science, this book imparts basic financial concepts irrespective of the institutional framework, ensuring that students learn about finance in a way that is applicable both now and into the future. Pedagogical features include learning objectives and major takeaways, applications in the world of business, numerous worked examples, key equation boxes highlighting the most important financial equations, quick check questions with solutions, key finance terms with a detailed glossary, and more than 380 homework problems. Online resources include a solutions manual, detailed instructor manual to adapt the book to your course, lectures slides and an 800 question test bank for instructors.
Conditionality Breeds Contempt: Donor and Multilateral Myopia in Sudan
Authors: Ali Muez , Alneel Muzan , Hassanain Mayada
Published: January 2025

Sudan’s political distortions under Bashir’s regime between 1989 and 2018 resulted in multiple economic crises and civil wars. After assuming office in 2019, the Transitional Government implemented economic reforms aiming to stabilize the economy. It sought support from donors and international financial institutions, who conditioned support on stringent conditions. Civil society publicly decried the economic reforms and warned of the implications of discounting Sudan’s political distortions. Ultimately, the military orchestrated a coup citing poor economic management. Sudan’s experience highlights the importance of contextual policymaking during political transitions and the limitations of the approach employed by donors and multilateral organizations.
Discovering sanctuaries for the Endangered thick-shelled river mussel Unio crassus in Kaliningradskaya Oblast, Russia
Authors: Popov Igor , Markovets Mikhail , Abakumov Evgeny
Published: January 2025

The thick-shelled river mussel Unio crassus is categorized as Endangered on the IUCN Red List, and searching for surviving populations is urgent. We surveyed for this species in Kaliningradskaya Oblast, a Russian territory lying between Poland and Lithuania, where empty shells of the species had been reported from two rivers. There are at least 125 rivers and numerous small streams in the region, and as a comprehensive survey of all of these watercourses is infeasible, we used a method developed for surveys of the freshwater pearl mussels Margaritifera margaritifera and Margaritifera laevis. This involved a remote assessment of the forests and lakes in the river basins to identify sites potentially suitable for U. crassus based on criteria used for pearl mussels, followed by site surveys. We surveyed six sites and discovered U. crassus in five of those, only two of which support healthy populations. The existence of other U. crassus populations in Kaliningradskaya Oblast is unlikely. This study underscores the critical role of riparian arboreal vegetation for freshwater mussels. The conservation of U. crassus in rivers surrounded by farmlands is challenging because of siltation, eutrophication and other processes that negatively impact the riverine environment. Even the abandonment of these farmlands does not necessarily lead to improvements in mussel survival. Any plans for the restoration of U. crassus will require concurrent restoration of riparian arboreal vegetation.
Coherence‐Based Characterization of a Long‐Period Monochromatic Seismic Signal
Authors: Takano Tomoya , Poli Piero
Published: January 2025

Continuous seismic data analysis identifies signals related to physical processes within the Earth or on its surface. Characterizing seismic signals yields insights into source processes and Earth's structural features. Global seismic network analysis of long‐period (25–100 s) surface waves has detected seismic events not identified through high‐frequency body wave analysis. However, detecting long‐lasting monochromatic signals with narrow spectral peaks, which carry valuable information about geological and environmental processes, remains challenging on a global scale. We developed a coherence‐based approach to characterize long‐period monochromatic signals on a global scale. In addition to signals originating from the Gulf of Guinea, Vanuatu islands, and a submarine volcano, we observed a previously unidentified signal originating from the Canadian Arctic, likely associated with glacier dynamics. Our approach explores long‐period monochromatic seismic signals in continuous seismic data, providing a foundation for future studies to characterize the physical processes generating these signals on Earth's surface.
3D Viscoelastic Models of Slip‐Deficit Rate Along the Cascadia Subduction Zone
Authors: Pollitz Fred F.
Published: January 2025

Interseismic deformation in the Pacific Northwest is constrained by the horizontal crustal velocity field derived from the Global Positioning System (GPS) in addition to vertical rates derived from GPS, leveling, and tide gauge measurements. Such measurements were folded in to deformation models of fault slip rates as part of the 2023 National Seismic Hazard Model update. Here I build upon one of the contributing models, the viscoelastic earthquake‐cycle model of Pollitz (2022, https://doi.org/10.1785/0220220137). This model permits inclusion of effects of time‐dependent viscoelastic relaxation within earthquake cycles (i.e., “ghost transients”) and laterally variable elastic and/or ductile material properties. I leverage these capabilities to incorporate the Cascadia megathrust into Western U.S.‐wide deformation models in which crustal fault slip rates are estimated simultaneously with slip deficit rates along the interplate boundary between the descending Juan de Fuca plate and North American plate. This effort includes construction of a margin‐wide model of viscoelastic structure founded on the Slab 2.0 model and probes different models of the ductile properties of the surrounding oceanic asthenosphere, continental lower crust, and mantle asthenosphere. This results in new estimates of the distribution of slip deficit rate along the  km long margin, highlights the importance of correcting for glacial‐isostatic adjustment effects, and permits assessment of sensitivity of results to assumed ductile properties.
Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia
Authors: Tremblay Cedric S. , Saw Jesslyn , Yan Feng , Boyle Jacqueline A. , Amarasinghe Ovini , Abdollahi Shokoufeh , Vo Anh N. Q. , Shields Benjamin J. , Mayoh Chelsea , McCalmont Hannah , Evans Kathryn , Steiner Anna , Parsons Kevin , McCormack Matthew P. , Powell David R. , Wong Nicholas C. , Jane Stephen M. , Lock Richard B. , Curtis David J.
Published: January 2025

Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3. Despite a highly proliferative state, these FLT3-overexpressing cells had long-term self-renewal capacity and almost complete resistance to chemotherapy. Chromatin immunoprecipitation and assay for transposase-accessible chromatin sequencing demonstrated FLT3 and its ligand may be direct targets of the LMO2 stem-cell complex. Media conditioned by Lmo2 transgenic thymocytes revealed an autocrine FLT3-dependent signaling loop that could be targeted by the FLT3 inhibitor gilteritinib. Consequently, gilteritinib impaired in vivo growth of ETP-ALL and improved the sensitivity to chemotherapy. Furthermore, gilteritinib enhanced response to the BCL2 inhibitor venetoclax, which may enable “chemo-free” treatment of ETP-ALL. Together, these data provide a cellular and molecular explanation for enhanced cytokine signaling in LMO2-driven ETP-ALL beyond activating mutations and a rationale for clinical trials of FLT3 inhibitors in ETP-ALL.
Theoretical and experimental investigations of the CMOS compatible Pirani gauges with a temperature compensation model
Authors: Xu Shizhen , Yang Gai , Chen Junfu , Jiao Rui , Wang Ruoqin , Yu Hongyu , Xie Huikai , Wang Xiaoyi
Published: January 2025

In this article, a CMOS-compatible Pirani vacuum gauge was proposed featuring enhanced sensitivity, lower detection limit, and high-temperature stability, achieved through the implementation of a surface micromachining method coupled with a temperature compensation strategy. To improve performance, a T-type device with a 1 µm gap was fabricated resulting in an average sensitivity of 1.10 V/lgPa, which was 2.89 times larger than that (0.38 V/lgPa) of a L-type device with a 100 µm gap. Additionally, FEA simulations were conducted, analyzing the influence of heater temperature on sensitivity and the attenuation of sensitivity across varying ambient temperatures. A semi-empirical theoretical mode was derived for performance prediction, demonstrating strong alignment with experimental results, underscoring its effectiveness in compensating for sensitivity attenuation. Building on the foundation, the device’s performance under different ambient temperatures was characterized and effectively compensated in two distinct operational modes: constant temperature mode and constant temperature difference mode (the whole range temperature compensation error can be controlled within 2.5%). Finally, the short-time stability (variation level is approximately 1 mV), noise floor (Vrms=384 μV) and detection limit (0.07 Pa @1 Hz) of the device were characterized, confirming its suitability for practical implementation.
Isolated congenital diaphragmatic hernia and three-year neurodevelopmental outcomes
Authors: Toyoshima Katsuaki , Aoki Hirosato , Katsumata Kaoru , Sato Yoshiaki , Inoue Hirosuke , Ito Miharu , Amari Shoichiro , Maruyama Hidehiko , Arahori Hitomi , Kondo Takuya , Kim Kiyokazu , Yamoto Masaya , Saito Tomoko , Okuyama Hiroomi , Usui Noriaki , Terui Keita , Nagata Kouji ,   on behalf of the Japanese Congenital Diaphragmatic Hernia Study Group
Published: January 2025

Background

To retrospectively investigate the developmental outcomes at 3 years of age in patients with congenital diaphragmatic hernia (CDH) using a multicenter collaborative research approach.

Methods

We evaluated patients with CDH and no other malformations born between 2010 and 2016 in seven facilities in the Japanese CDH Research Group. The developmental quotient (DQ) at 3 years of age was evaluated using the Kyoto Scale of Psychological Development 2001, the most standardized scale in Japan. Factors associated with a DQ score < 85 were also analyzed.

Results

Of 196 patients, developmental assessments at 3 years of age were performed in 132 patients (67%). Among these, 99 patients (75%) had a DQ score ≥ 85, 25 (19%) had a DQ score between 70 and 84, and 8 (6%) had a DQ score < 70. Multivariate analysis showed that the observed/expected lung area-to-head circumference ratio was an independent predictor of a DQ score < 85, with an adjusted odds ratio of 0.62 (95% confidence interval: 0.40–0.96; p = 0.03).

Conclusion

Generally, isolated CDH is associated with good developmental outcomes for survivors, even after intensive care. However, there is a risk of neurodevelopmental impairment if pulmonary hypoplasia is present.

Impact

This research highlights the observed/expected lung area-to-head circumference ratio (o/e LHR) as a crucial indicator to predict neurodevelopmental outcomes in 3-year-old children diagnosed with isolated congenital diaphragmatic hernia (CDH).

Our results provide robust evidence from a large multicenter cohort, emphasizing the importance of o/e LHR in early risk stratification and prolonged neurodevelopmental follow-up.

These findings highlight the need for comprehensive management and tailored follow-up care in CDH patients, potentially improving clinical protocols and enhancing the quality of life and outcomes for affected children.
Multi-locus inherited neoplasia alleles syndromes in cancer: implications for clinical practice
Authors: Yuen Jeanette , Zhou Siqin , Caeser Rebecca , Venkatramani Mallika , Bte Ishak Diana Nur , Li Shao-Tzu , Zhang Zewen , Chiang Jianbang , Chan Sock Hoai , Ngeow Joanne
Published: January 2025

The popularity of multi-gene testing has identified more families with two or more pathogenic variants (PV) in cancer predisposition genes, also known as ‘MINAS’ (multilocus inherited neoplasia alleles syndromes). They are at risk of suboptimal treatment and management as little on this topic is known. We conducted a systematic review of published MINAS cases within cancer predisposition genes to understand their association with more severe presentations. We analysed 413 MINAS carriers, which included 33 novel cases from the Cancer Genetics Service, National Cancer Centre Singapore. Statistical tests were conducted to assess association between carrier characteristics and the number PV identified. Results suggest that MINAS carriers have more malignancies (31.7% vs 21.5% vs 10.3% %; p < 0.001), a younger median age of first cancer diagnosis (40.0 vs. 44.0 vs. 49.0 years; p < 0.001) and an early onset of cancer (defined as <5% PV-associated cancer risk at age of diagnosis) (24.9% vs 7.7% vs 4.7%; p < 0.001) compared to monoallelic and non-carriers. We also studied the association of clinical characteristics by the dominant or recessive nature of PV harboured, where more dominant-dominant (D-D) carriers reported multiple malignancies (34.0%), compared to dominant-recessive (D-R) (23.9%) and recessive-recessive (R-R) carriers (20%;) (p = 0.051). Our findings suggest that MINAS carriers are prone to more and younger malignancies and the dominant or recessive nature of PV within double carriers can affect clinical presentation. We suggest a framework to guide management based on the dominant or recessive nature of PV within double PV carriers.
3D numerical modeling of the deformation and failure mechanisms of batter pile groups subjected to fault ruptures
Authors: Soomro Mukhtiar Ali , Zhu ZiQing , Aslam Muhammad Shamrooz , Bilal Hazrat , Yahya Abid , Badruddin Irfan Anjum
Published: January 2025

Fault ruptures induced by earthquakes pose a significant threat to constructions, particularly underground structures such as pile foundations. Among various foundation types, batter pile foundations are widely used due to their ability to resist inclined forces. To gain new insights into the response of batter pile groups to fault ruptures caused by earthquakes, this study investigates the deformation and failure mechanisms of batter pile groups due to the propagation of normal and reverse fault ruptures using 3D numerical modeling. An advanced hypoplastic constitutive model for clay, which accounts for small-strain stiffness, and a concrete damage plasticity (CDP) model are employed to simulate the soil and the batter pile foundation, respectively. Results show that following fault propagation, nearly 10% tilting and significant displacement occurred at the pile cap, indicating a total failure of the batter pile foundation. It was also observed that the piles bent towards the slipping direction of the hanging wall. Tensile damage to the pile foundation was notably more severe than compression damage. The most severely damaged regions were not only located at the joints between the piles and the pile caps but were also found along the pile shafts.
Relationships between structural stigma, societal stigma, and minority stress among gender minority people
Authors: Clark Kristen D. , Lunn Mitchell R. , Sevelius Jae M. , Dawson-Rose Carol , Weiss Sandra J. , Neilands Torsten B. , Lubensky Micah E. , Obedin-Maliver Juno , Flentje Annesa
Published: January 2025

Structural stigma towards gender minority (GM; people whose current gender does not align with sex assigned at birth) people is an important contributor to minority stress (i.e., stress experienced due to one’s marginalized GM identity), although existing variables are unclear in their inclusion of social norms, or societal stigma, as a key component of the construct. We examined potential variables representing structural stigma, including variables that are inclusive of societal stigma, to identify those that most strongly relate to minority stress outcomes. We tested variables identified in the literature as measures of structural stigma inclusive of societal stigma (LGBT + Business Climate Index, state voting behaviors, and Google Trends search data), the most commonly used structural stigma variable (State Policy Environment Tally), and proxy variables (region, population density) for comparison. The relationships between structural stigma and minority stress model outcomes were tested in a sample of GM participants from The Population Research in Identity and Disparities for Equality (PRIDE) Study (N = 2,094) 2019 Annual Questionnaire using a structural equation model (SEM). Lower structural stigma (i.e., higher LGBT Business Climate Index) was associated with lower experienced stigma (β= -0.260, p < .01) and lower anticipated stigma (β= -0.433, p < .001). Greater conservative voting behavior was associated with less experienced stigma (β= -0.103, p < .01). Living in a more densely populated county was also associated with lower anticipated stigma (β=-0.108, p < .001) and greater identity outness (β = 0.053, p < .05). Two of the identified structural stigma variables that were inclusive of societal stigma (i.e., LGBT + Business Climate Index, conservative voting behaviors) and one proxy variable (population density) were associated with minority stress outcomes. However, the most commonly used variable for structural stigma (State Policy Environment Tally) was not associated with any outcomes. The State LGBT + Business Climate Index showed the most promise for use as a structural stigma variable in future research. The application of this variable should be investigated further to explore its association with health outcomes and to inform efforts to reduce health equity barriers experienced by GM people through addressing structural stigma in a manner inclusive of societal stigma.
Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling
Authors: Wei Wei , Li Xionghao , Hou Ning , Xie Aowei , Liang Huicong , Gao Ting , Jing Xiaoli , Li Liqin , Hao Jiejie , Xu Ximing
Published: January 2025

Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these reactions, NATs play a pivotal role in the detoxification and metabolic processing of a wide range of drugs and carcinogens. NAT in marine V. vulnificus plays a role in the metabolism of drugs, leading to the development of drug resistance in marine V. vulnificus. However, inhibitors targeted marine V. vulnificus NAT [(VIBVN)NAT] remain unclear. Therefore, our research aimed to identify potential hit compounds that target (VIBVN)NAT. We integrated multiple computational approaches to screen for effective inhibitors. From this process, we identified two hit compounds, AK-968-11563024 and AG-205-36710025, with IC50 values of 18.86 µM and 33.27 µM, respectively. Molecular dynamics simulations further elucidated the binding mechanism between (VIBVN)NAT and AK-968-11563024. Our study revealed that AK-968-11563024 forms stable interactions with PHE124, HIS167, and TRP230, which may contribute to its biological activity. Our findings provide a valuable foundation for the future development of drugs targeted therapeutics against (VIBVN)NAT.
Determining interaction directionality in complex biochemical networks from stationary measurements
Authors: Leibovich N.
Published: January 2025

Revealing interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Some methods may reveal undirected network topology, e.g., using node-node correlation. Yet, the direction of the interaction, thus a causal inference, remains to be determined - especially in steady-state observations. We introduce a method to infer the directionality within this network only from a “snapshot” of the abundances of the relevant molecules. We examine the validity of the approach for different properties of the system and the data recorded, such as the molecule’s level variability, the effect of sampling and measurement errors. Simulations suggest that the given approach successfully infer the reaction rates in various cases.
Predicting construction waste in Egyptian residential projects: a robust multiple regression model approach
Authors: KhairEldin Mohamed , Daoud Ahmed Osama , Ibrahim Ahmed Hussein , Toma Hossam M.
Published: January 2025

Effective construction waste (CW) management, mainly concrete, brick, and steel, is a critical challenge due to its significant environmental and economic impacts. This study addresses this challenge by proposing multiple linear regression models to predict waste generation in residential buildings within the Egyptian construction industry, considering the influence of factors such as building design and site management features. Using data from 25 case studies, the models demonstrated high predictive accuracy, with adjusted R² values of 0.877, 0.893, and 0.889 for concrete, bricks, and steel waste, respectively. These R2 values indicate that the models explain approximately 88–89% of the variance in waste generation in residential buildings, highlighting their effectiveness in enhancing resource planning and waste management strategies. The findings suggest that incorporating variables such as total area, design consistency, and site organization significantly improves the accuracy of waste predictions. Although the models show acceptable performance, future research should aim to expand the dataset, incorporate additional variables, and test the models across different types of construction projects to validate further and refine these predictive tools. The models offer valuable insights for enhancing construction practices, minimizing waste, and supporting sustainable development in Egypt’s construction industry. With accurate forecasts of waste generation, the models help project managers and stakeholders to plan CW more effectively, mitigating unnecessary material consumption and reducing environmental impacts. These findings help to adopt sustainable construction practices, such as improved recycling processes and decreased dependence on landfills, to support Egypt’s Vision 2030.
Hormone circuit explains why most HPA drugs fail for mood disorders and predicts the few that work
Authors: Milo Tomer , Nir Halber Shiraz , Raz Moriya , Danan Dor , Mayo Avi , Alon Uri
Published: January 2025

Elevated cortisol in chronic stress and mood disorders causes morbidity including metabolic and cardiovascular diseases. There is therefore interest in developing drugs that lower cortisol by targeting its endocrine pathway, the hypothalamic–pituitary–adrenal (HPA) axis. However, several promising HPA-modulating drugs have failed to reduce long-term cortisol in mood disorders, despite effectiveness in other hypercortisolism conditions such as Cushing’s syndrome. The reasons for these failures remain unclear. Here, we use a mathematical model of the HPA axis to demonstrate that the pituitary and adrenal glands compensate for drug effects by adjusting their functional mass, a feedback mechanism absent in Cushing tumors. Our systematic in silico analysis identifies two interventions targeting corticotropin-releasing hormone (CRH) as effective for lowering long-term cortisol. Other targets either fail due to gland mass compensation or harm other aspects of the HPA axis. We propose CRH-neutralizing antibodies and CRH-synthesis inhibitors as potential targets for reducing long-term cortisol in mood disorders and chronic stress. More generally, this study indicates that understanding the slow compensatory mechanisms in endocrine axes can be crucial to prioritize drug targets.
Effects of supplementation of macular pigment carotenoids on ocular health: a Raman spectroscopic study of human blood serum of glaucoma patients
Authors: Udensi Joy , Loughman James , Loskutova Ekaterina , Byrne Hugh J.
Published: January 2025

Supplementing glaucoma patients with macular pigment carotenoids improved ocular health, as confirmed by Serum Raman spectroscopy correlating with MPOD and ocular parameters. This highlights vast potential benefits of the method for  healthcare.