bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding phage BX-1 resistance in
Vibrio alginolyticus
AP-1 and the role of quorum-sensing regulation
Authors: Li Xiaoyu , Liu Xin , Ma Tianyi , Su Haochen , Sui Bingrui , Wang Lili , Murtaza Bilal , Xu Yongping , Li Na , Tan Demeng
Published: January 2025

The marine ecosystem is characterized by a rich diversity of bacterial hosts and their phages. The propagation of phages is primarily limited by their ability to adsorb to host cells and is further challenged by various bacterial defense mechanisms. To fully realize the potential of phage therapy in aquaculture, a comprehensive understanding of phage-host interactions and their regulation is essential. In this study, we isolated a novel
Myoviridae
phage, BX-1, capable of infecting
Vibrio alginolyticus
AP-1, and characterized its resistant mutants. We elucidated the essential role of the bacterial cellulose biosynthesis-related gene
bcsE
, which functions as a cyclic di-GMP-binding protein, in influencing host susceptibility to phage BX-1. Interestingly, Congo Red, Calcofluor White staining, and cellulose content assays indicated that deletion of
bcsE
in strain AP-1 does not completely abolish cellulose production, suggesting that
bcsE
is not essential for bacterial cellulose synthesis. Furthermore, investigating the signaling molecules that regulate phage-host interactions, we find that in a high cell density state (Δ
luxO
), bacterial cells upregulate their susceptibility to phage BX-1, which leads to a rapid development of resistance. Conversely, cells in a low-density state (Δ
hapR
) exhibit reduced susceptibility to phage BX-1 while still producing comparable phage progenies. This population density-dependent response is primarily enhanced by the predicted quorum-sensing autoinducer CAI-1, synthesized by the gene
cqsA
. Collectively, our findings reveal the intricate dynamics of phage-host interactions, adding a new layer of complexity to our understanding of phage receptor regulations.

IMPORTANCE

Phage therapy has garnered significant attention as a promising solution to antibiotic resistance in aquaculture. However, its application is hindered by a limited understanding of the genotypic and phenotypic dynamics governing phage-host interactions. Bacteria have developed various defense mechanisms against phages, such as mutations in phage receptors. In this study, we demonstrate that the bacterial cellulose biosynthesis-related gene
bcsE
plays a crucial role in determining susceptibility to phage BX-1, while quorum-sensing (QS) systems significantly influence collective phage-related behaviors. By characterizing the mechanisms of phage resistance and the regulatory role of QS in susceptibility, our findings enhance the understanding of phage-host interactions and pave the way for more effective phage therapy applications. Collectively, these insights illuminate the evolutionary complexities of phage-defense systems and the broader strategies that bacteria employ to coexist with phages.
Human chorionic gonadotropin-secreting osteosarcoma
Authors: Sanchez Natalia Gabriela , Horvai Andrew E , Zacco Emanuela , Monga Varun
Published: January 2025

Secretion of beta human chorionic gonadotropin (β-hCG) is a rare, recently recognised paraneoplastic syndrome. Herein, we present a case of a woman in her 30s with right femur conventional high-grade osteosarcoma and a positive screening urine pregnancy test. Subsequent workup failed to reveal an intrauterine or extrauterine pregnancy. Rather, pathology and gene expression studies confirmed serum β-hCG production by osteosarcoma cells. Though the prognostic implications of β-hCG expression are unclear, β-hCG may be a useful surveillance marker to monitor disease progression or recurrence.
Rare occurrence of upper-limb ischaemia necessitating transhumeral amputation following axillary arterial line placement
Authors: Boland Allison Clare , Joseph-Mofford Genevieve , Pino Cassandra , Levine Diane , Tennenberg Steven D , Vaidya Rahul
Published: January 2025

Arterial cannulation, commonly performed in the radial artery, is a widely used method for continuous blood pressure monitoring. Occasionally, the axillary artery is used as an alternate site of cannulation. However, complications like occlusion can lead to adverse events and severe outcomes. We present a case of axillary arterial line placement resulting in ischaemic limb injury and amputation, highlighting the need to recognise risk factors.

A woman in her mid-60s underwent a lobectomy for adenocarcinoma of the lung and suffered postoperative complications resulting from arterial line placement. Despite interventions, she developed progressive ischaemia of her left upper limb, necessitating amputation. This case highlights the risks associated with arterial catheterisation and potential adverse outcomes, offering recommendations for arterial line placement in high-risk patients.
Triple spinal dural arteriovenous fistula
Authors: Boeris Davide , Giordano Martina , Petrella Giacomo , Cenzato Marco
Published: January 2025

Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal vascular malformations. Multiple SDAVFs are unusual and can occur either synchronously or metachronously, as reported in the literature. We report on the unusual case of a woman with three separate SDAVFs, which were surgically treated within the same setting; the postoperative course was characterised by unexplained repeated haematoma formation within the surgical sites. A review of the literature was performed to assess the outcomes of patients with multiple distinct SDAVFs: the data of 19 patients were collected, accounting for 41 SDAVFs. Of these, only two patients had all the SDAVFs treated within the same surgical procedure. Based on our literature review, contemporary surgery is not a predisposing factor to haemorrhage per se; however, we can hypothesise that the uncontrolled deliquoration could account for haematoma formation within the surgical sites.
Ileo-ileal intussusception and necrotising enterocolitis after indomethacin exposure masquerading clinically as solitary intestinal perforation
Authors: Tu Irene Wen Hui , Chan Esther Ern Hwei , Laksmi Narasimhan Kannan
Published: January 2025

We report a case of small bowel perforation from ileo-ileal intussusception with necrotising enterocolitis (NEC) after indomethacin exposure mimicking spontaneous intestinal perforation in an extremely preterm neonate. Indomethacin exposure can cause mesenteric hypoperfusion, resulting in an ischaemic lead point for intussusception and NEC. We advocate that intussusception should be considered as one of the differentials for neonates with recurrent feeding intolerance postindomethacin exposure. Diagnosis with early ultrasound by an experienced sonographer is crucial for timely surgical reduction to prevent intestinal perforation.
Disparities in dolutegravir utilisation in children, adolescents and young adults (0–24 years) living with HIV. An analysis of the IeDEA Pediatric West African cohort
Authors: Desmonde Sophie , Dame Joycelyn , Malateste Karen , David Agatha , Amorissani-Folquet Madeleine , N'Gbeche Sylvie , Sylla Mariam , Takassi Elom , Eboua François Tanoh , Kouakou Kouadio , Bagnan Tossa Lehila , Yonaba Caroline , Leroy Valeriane
Published: January 2025

Introduction

We describe the 24-month incidence of Dolutegravir (DTG)-containing antiretroviral treatment (ART) initiation since its introduction in 2019 in West Africa.

Methods

We included all patients aged 0–24 years on ART from nine clinics in Côte d’Ivoire (n=4), Ghana, Nigeria, Mali, Benin, and Burkina Faso. Baseline varied by clinic and was defined as date of first DTG prescription; patients were followed up until database closure/death/loss to follow-up (LTFU, no visit ≥7 months), whichever came first. We computed the cumulative incidence function for DTG initiation; associated factors were explored in a shared frailty model, accounting for clinic heterogeneity.

Results

Since 2019, 3350 patients were included; 47.2% were female; 78.9% had been on ART ≥12 months. Median baseline age was 12.5 years (IQR 8.4–15.8). Median follow-up was 14 months (IQR 7–22). The overall cumulative incidence of DTG initiation reached 22.7% (95% CI 21.3 to 24.2) and 56.4% (95% CI 54.4 to 58.4) at 12 and 24 months, respectively. In univariate analyses, those aged <5 years and female were overall less likely to switch. Adjusted on ART line and available viral load (VL) at baseline, females aged >10 years were less likely to initiate DTG compared with males of the same age (adjusted HR among 10–14 years: 0.62, 95% CI 0.54 to 0.72; among ≥15 years: 0.43, 95% CI 0.36 to 0.50), as were those with detectable VL (>50 copies/mL) compared with those in viral suppression (aHR 0.86, 95% CI 0.77 to 0.97) and those on PIs compared with those on non-nucleoside reverse-transcriptase inhibitors (aHR after 12 months of roll-out: 0.75, 95% CI 0.65 to 0.86).

Conclusion

Paediatric DTG uptake was incomplete and unequitable in west African settings: DTG use was least likely in children <5 years, females ≥10 years and those with detectable VL. Maintained monitoring and support of treatment practices is required to better ensure universal and equal uptake.
Weal and woe of interleukin-18 in the T cell therapy of cancer
Authors: Kessel Christoph , Rossig Claudia , Abken Hinrich
Published: January 2025

Chimeric antigen receptor (CAR) T cell therapy of solid cancer remains below expectations; adding cytokine help through IL-18 has shown remarkable efficacy in first clinical trials. As IL-18 is also a powerful driver of hyperinflammatory conditions, we discuss to what extent unleashing IL-18 is a double-edged sword in CAR T cell therapies.
Characterization of individuals achieving type 2 diabetes remission in real-world settings: bridging clinical evidence and patient experiences
Authors: Marcotte-Chénard Alexis , Oliveira Barbara , Rahman Tahmina , McKelvey Sean , Elliott Tom , Rocha Paula , Mackay Dylan , Little Jonathan P.
Published: January 2025

The objectives of the study were to (1) describe characteristics and lifestyle factors of individuals who have achieved type 2 diabetes (T2D) remission (sub-diabetes glucose levels without glucose-lowering medications for ≥3 months) through changes to diet and exercise behaviour in real-world settings; (2) investigate continuous glucose monitoring (CGM) profiles of these individuals and explore how dietary pattern may influence glucose regulation metrics. This cross-sectional study recruited individuals living with T2D who achieved remission via changes to diet or exercise behaviours. Various questionnaires were used to assess overall health and participants wore a blinded CGM for 14 days to assess glucose profiles and filled out 3-day food records. A total of 21 adults (57 ± 8 years of age) who were recently diagnosed with T2D (4 ± 3 years) with a A1c of 5.7 ± 0.4% volunteered to participate. Participants achieved remission through various means (e.g., combination of diet and exercxise/physical activity) and self-reported following different diets, including 52% following a low-carbohydrate or very low carbohydrate diet, 14% following a “ketovore/carnivore” diet, 10% using a meal replacement diet, 5% following Weight Watcher’s diet, and 19% no defined dietary pattern. The 24 h average CGM glucose value was 5.0 [4.8–5.6] mmol/L (median [IQR]) with 92 [85–97]% of time spent in range (between 4.0 and 9.9 mmol/L). The 24 h average CGM glucose ( r = 0.692; P = 0.001) and A1c ( r = 0.470; P = 0.049) were correlated with the daily percentage of energy intake from carbohydrate. Remission of T2D appears achievable through various means, including adoption of different dietary approaches and a more active lifestyle underpinning the importance of a patient-centred care.
A simplified soil-structure interaction model for load-settlement analysis of piles
Authors: Pham Tuan A. , Akan Recep , Tabaroei Abdollah
Published: January 2025

The full skin friction and full end-bearing of a single pile are not mobilized at the same displacement while the conventional approach often oversimplifies by adding the skin friction to the end-bearing resistance as independent calculation steps. This paper presents a simplified interaction approach for the nonlinear load-settlement analysis of a single pile considering simultaneously the degradation of skin friction resistance and end-bearing resistance hardening under varying loads. The ability to estimate the load-settlement response of piles based on either needed loads or settlement is a special benefit of the proposed approach over existing methods. In addition, the proposed model is able to separate the skin friction resistance, end-bearing resistance and elastic compression at arbitrary settlement. The analytical method shown a satisfactory performance as compared to experimental results for three extensively studied field test situations. The suggested approach shows promise as a suitable solution for the design optimization as well as the preliminary analysis to organize a suitable loading test program. A parametric analysis is conducted to further examine the influence of various significant parameters related to the load-settlement response of piles.
Grizzly bears detected at ecotourism sites are less likely than predicted by chance to encounter conflict
Authors: Field Kate A. , Moody Jason E. , Levi Taal , Darimont Chris T.
Published: January 2025

Whether ecotourism can lead to human–wildlife conflict is not well understood. In Nuxalk Territory, grizzly bear ( Ursus arctos horribilis Ord, 1815) conflict occurred ∼41–58 km downstream from ecotourism. We screened for genetic matches between individuals that encountered conflict ( n = 30) and 118 individuals detected upstream via hair snags (including 34 at ecotour sites). Of these 34, one encountered conflict. In analysis Scenario 1, we considered all detected and undetected bears in the region as freely mixing, and used Bayes’ theorem to account for imperfect detection of ecotour bears among conflict samples, deriving an estimate of 1.47 (rounded to 2). Accounting for this uncertainty, we used a probability approach to ask how large the unknown non-ecotour bear population would have to be to observe this frequency of conflict among ecotour bears (2/34) by chance. The resulting population level exceeded available estimates, suggesting ecotour bears are less likely to encounter conflict. In Scenario 2, we assumed that downstream bears are not necessarily from the same population as those sampled upstream; we compared the proportions of known ecotour and non-ecotour bears among conflict samples and found no evidence of a significant difference. Collectively, these analyses suggest other human-caused drivers of conflict.
NUMERICAL ANALYSIS OF A FRACTIONAL MICRO/NANOBEAM-BASED MICRO-ELECTROMECHANICAL SYSTEM
Authors: ZHENG SHAOQING , CHEN LEI , LU JUNFENG
Published: January 2025

This paper focuses on considering a combined method for solving a fractional oscillation equation arising from a micro/nanobeam-based micro-electromechanical system under the magnetic force. It is an efficient method based upon the fractional complex transformation and the spreading residue harmonic balance method. The fractional oscillator is transformed as the conventional oscillation system by using the fractional complex transformation. The approximated periodic solutions and frequencies are given by applying the spreading residue harmonic balance method. Sensitive analysis of the approximated frequencies concerning different amplitudes and parameters is provided, which may be helpful for realizing the system stability. Numerical comparisons with some existing methods such as Runge–Kutta method and He’s frequency formulation approach are shown to confirm the efficiency of the proposed method.
Time–Frequency Dispersion Entropy Plane and its Application in Mechanical Fault Diagnosis
Authors: Zhang Fan , Shang Pengjian , Yin Yi
Published: January 2025

Fourier transform and entropy are two essential mathematical tools, and they have a fruitful role in system dynamics and machine learning research. In this paper, we propose a generalized composite multiscale amplitude dispersion entropy (GCMADE) and time–frequency dispersion entropy plane. GCMADE measures the complexity of the frequency domain of a time series and can approach the zero complexity of periodic sequences, unlike most other entropy methods. The time–frequency dispersion entropy plane further extracts time domain and frequency domain features of complex signals simultaneously through entropy. Its ability to measure the uncertainty of complex systems is analyzed by simulated data, and the results show that it can effectively distinguish between periodic sequences, chaotic sequences and stochastic processes. Finally, we introduce support vector machine (SVM) to perform mechanical fault diagnosis on five datasets. Compared with the other six algorithms, our method has significantly higher accuracy.
Model-Driven Deep Neural Network for Enhancing Direction Finding with Commodity 5G gNodeB
Authors: Liu Shengheng , Mao Zihuan , Li Xingkang , Pan Mengguan , Liu Peng , Huang Yongming , You Xiaohu
Published: January 2025

Pervasive and high-accuracy positioning has become increasingly important as a fundamental enabler for intelligent connected devices in mobile networks. Nevertheless, current wireless networks heavily rely on pure model-driven techniques to achieve positioning functionality, often succumbing to performance deterioration due to hardware impairments in practical scenarios. Here we reformulate the direction finding or angle-of-arrival (AoA) estimation problem as an image recovery task of the spatial spectrum and propose a new model-driven deep neural network (MoD-DNN) framework. The proposed MoD-DNN scheme comprises three modules: a multi-task autoencoder-based beamformer, a coarray spectrum generation module, and a model-driven deep learning-based spatial spectrum reconstruction module. Our technique enables automatic calibration of angular-dependent phase error thereby enhancing the resilience of direction-finding precision against realistic system non-idealities. We validate the proposed scheme both using numerical simulations and field tests. The results show that the proposed MoD-DNN framework enables effective spectrum calibration and accurate AoA estimation. To the best of our knowledge, this study marks the first successful demonstration of hybrid data-and-model-driven direction finding utilizing readily available commodity 5G gNodeB.
Deep PackGen: A Deep Reinforcement Learning Framework for Adversarial Network Packet Generation
Authors: Hore Soumyadeep , Ghadermazi Jalal , Paudel Diwas , Shah Ankit , Das Tapas , Bastian Nathaniel
Published: January 2025

Recent advancements in artificial intelligence (AI) and machine learning (ML) algorithms, coupled with the availability of faster computing infrastructure, have enhanced the security posture of cybersecurity operations centers (defenders) through the development of ML-aided network intrusion detection systems (NIDS). Concurrently, the abilities of adversaries to evade security have also increased with the support of AI/ML models. Therefore, defenders need to proactively prepare for evasion attacks that exploit the detection mechanisms of NIDS. Recent studies have found that the perturbation of flow-based and packet-based features can deceive ML models, but these approaches have limitations. Perturbations made to the flow-based features are difficult to reverse-engineer, while samples generated with perturbations to the packet-based features are not playable.

Our methodological framework, Deep PackGen, employs deep reinforcement learning to generate adversarial packets and aims to overcome the limitations of approaches in the literature. By taking raw malicious network packets as inputs and systematically making perturbations on them, Deep PackGen camouflages them as benign packets while still maintaining their functionality. In our experiments, using publicly available data, Deep PackGen achieved an average adversarial success rate of 66.4% against various ML models and across different attack types. Our investigation also revealed that more than 45% of the successful adversarial samples were out-of-distribution packets that evaded the decision boundaries of the classifiers. The knowledge gained from our study on the adversary’s ability to make specific evasive perturbations to different types of malicious packets can help defenders enhance the robustness of their NIDS against evolving adversarial attacks.
A Roadmap to Graph Analytics
Authors: Bonifati Angela , Ozsu M. Tamer , Tian Yuanyuan , Voigt Hannes , Yu Wenyuan , Zhang enjie
Published: January 2025

Graphs are ubiquitous data structures used in a large spectrum of applications, spanning from transportation networks, financial networks, social networks, product-order transactions and biomedical applications [33]. A recent survey on the usage of graph applications from real users has highlighted the fact that analytics is the most time-consuming task as opposed to testing, cleaning and ETL [32].
Influence of pH on Indium Deposition Rates: A Comprehensive Electrochemical Analysis
Authors: Pasha A. F. , Larson Z. I. , Borgesen P. , Dimitrov N.
Published: January 2025

Binary indium-tin (In-Sn) and ternary indium-tin-bismuth (In-Sn-Bi) alloys hold significant promise for reducing soldering temperatures in electronic assembly. However, traditional metallurgical methods are unsuitable for fabricating micro-solder joints, making alloy electroplating essential for fine-pitch interconnects. The co-electroplating of alloy constituents is often hindered by substantial differences in reduction potentials. Therefore, sequential electroplating followed by high-temperature reflow emerges as a more practical solution. Nonetheless, challenges persist, particularly due to the limited understanding of indium (In) deposition kinetics and its strong dependence on pH. This study investigates the influence of pH on In plating rates and overall deposition kinetics. The thickness and cross-sectional morphology of electroplated In films are analyzed across a pH range of 2.2–3.3, with plating conditions optimized to identify the most effective parameters. Structural properties, uniformity, and potential oxide inclusions in the electroplated films are assessed using X-ray diffraction and differential scanning calorimetry. Plating at pH 2.9 in a solution of 0.12 M In2(SO4)3 and 0.70 M Na2SO4 produces the highest deposition rate and the most structurally homogeneous layers. Deviations from this optimal pH inevitably promote side reactions that markedly reduce deposition rates and compromise film quality.
A Novel In Situ Scratching EC-ICP-MS Setup for Real Time Monitoring of Tribocorrosion and Repassivation Dynamics
Authors: Kalchgruber Lukas , Mears Laura L. E. , Handerkas Harald , Hahn Michael , Rester Martin , Weissensteiner Christian , Valtiner Markus
Published: January 2025

Tribochemical processes occur in various environments, where the combination of mechanical stress and chemical reactions can lead to significant changes in material properties, surface composition, roughness and technological performance. A detailed observation of chemical and mechanical tribodegradation, as well as materials repassivation are difficult to asses in-situ. Here, we developed a novel electrochemical flow cell to enable in-situ surface scratching followed by elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS). The cell features an eccentrically positioned rotating sphere that scratches the surface, while ICP-MS analyzes material degradation downstream. This facilitates both qualitative and quantitative assessments of the electrochemical and mechanical removal of material, and allows a quantitative characterization of repassivation. Experiments conducted on a stainless steel sample, Fe(82.5)Cr(17.5), demonstrated excellent reproducibility. Due to tribomechanical damaging, repassivation of damaged areas showed considerably faster first order reaction kinetics and higher dissolution rates, compared to electrochemical passivation. During the scratching process, both ions and particles were observed to dissolve. While high Cr-content (≥12%) facilitates full repassivation, low Cr-content (< 12%) samples are unable to form a stable passive layer under tribocorrosive conditions. This technique is directly applicable for analyzing complex tribochemical processes, which can apply to a wide range of available engineering materials.
CeO2/MWCNT/Carbon Black Modified Electrode for Improving the Performance of Electrochemical Nitrite Sensor
Authors: Ding Saiwen , Ao Jialin , Shu Ting
Published: January 2025

CeO2 was synthesized and combined with different types of carbon nanomaterials such as carboxylated multiwalled carbon nanotubes (c-MWCNT) and carbon black (CB) for electrochemical detection of nitrite. The composite (c-MWCNT/CB/CeO2) showed the best sensing performance. It was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscpy, Brunnauer-Emmett-Teller, and Raman spectroscopy. The electrochemical performance of the c-MWCNT/CB/CeO2 modified fluorine-doped tin oxide (FTO) glass and glassy carbon electrode (GCE) was studied. The optimized c-MWCNT/CB/CeO2/FTO sensor exhibited a linear range of 0.01–13 mM, a sensitivity of 231.4 μA·mM−1·cm−2, and a detection limit of 0.59 μM, while the c-MWCNT/CB/CeO2/GCE sensor showed a linear range of 0.01–33 mM, a sensitivity of 340.5 μA·mM−1·cm−2, and a detection limit of 0.45 μM. In addition, the sensor had good stability, reproducibility and selectivity. More importantly, it was successfully used for nitrite detection in green tea samples, indicating its feasibility.
Photon-Assisted Synchronization of Molecular Electrochemical Oscillators
Authors: Kernbach Serge
Published: January 2025

Formation of hydronium and carbonate ions from carbon dioxide in the aqueous phase is a reversible process and can both produce and consume ions. These equilibrium reactions represent molecular electrochemical oscillators in pure water. Reversible switching of ionic dynamics is a chaotic process, which is influenced by the CO2 level, temperature, concentration of decay products, magnetic fields and other factors. As demonstrated in previous works, weak variations of magnetic fields induce different electrochemical reactivity and generate ionic waves caused by mutual synchronization of molecular oscillators. Such waves correlate between transparent electrochemical cells, suggesting macroscopic mechanisms for their interaction. This work explores these observations by monitoring the high-resolution ionic dynamics and temperature of independent fluidic cells with electrochemical impedance spectroscopy. The occurrence of synchronization is studied in 4-16 cells grouped in one or several non-transparent thermo-insulating containers; about 20 million of samples are analyzed. Synchronization effects are shown to occur primarily in the CO2 dissolving scenario on the 3-10 minute scale. Without CO2 access, mutual synchronization is either non-existent or negligible. Maximal correlations with r > 0.9 are achieved between 4-6 cells with one synchronization event per 8000 samples; with r > 0.7—in up to 8-10 cells with one event per 3000 samples. The number of synchronization events is about five times lower when cells are separated between non-transparent containers. We also noted a generation of in-phase and anti-phase temperature-impedance waves highly synchronized between independent cells. To explain such results, we consider the hypothesis of molecular quantum networks that operate with spin conversion of water isomers, where photon-assisted entanglement introduces weak coupling between oscillators. Since spin-level phenomena are involved into macroscopic synchronization, investigation of these mechanisms can lead to new quantum sensing technologies.
The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Activity with KRASG12C Inhibitors in Preclinical Models
Authors: Jameson Nathan M. , Kim Daehwan , Lee Catherine , Skrable Blake , Shea Alexandra , Guo Xiao , Izadi Hooman , Abed Mona , Harismendy Olivier , Ma Jianhui , Kim Doris S. , Lackner Mark R.
Published: January 2025

Kirsten rat sarcoma (KRAS) is a potent oncogenic driver that results in the downstream hyperactivation of MAPK signaling while simultaneously increasing replication stress (RS) and accumulation of DNA damage. KRASG12C mutations are common and targetable alterations. Therapeutic inhibition of KRASG12C and eventual resistance to these inhibitors are also known to drive RS and DNA damage through adaptive mechanisms that maintain addiction to high MAPK signaling. High levels of RS result in a stronger reliance on cell-cycle checkpoints, thereby introducing a vulnerability to inhibition of cell-cycle checkpoint regulators such as the WEE1 kinase. This provides a rationale for combining azenosertib, a novel, selective, and orally bioavailable WEE1 inhibitor, with KRASG12C inhibitors. An in vitro combination of azenosertib with multiple KRASG12C inhibitors demonstrated synergistic cell growth inhibition across a panel of KRASG12C cell lines in both 2D and 3D assays. In vivo studies demonstrated that azenosertib exhibited significant monotherapy activity as well as synergistic tumor growth inhibition (TGI) when combined with KRASG12C inhibitors, including tumor regression in cell-derived xenograft models of non–small cell lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. Importantly, KRASG12C inhibitor–resistant cell-derived xenograft and patient-derived xenograft models demonstrated synergistic TGI in combination arms. Finally, analysis of biomarkers from in vitro and in vivo tumor samples displayed increases in protein markers of RS, DNA damage, and apoptosis after combination treatment. Taken together, our results suggest that the combination of azenosertib with KRASG12C inhibitors enhances TGI over single-agent therapy and may be an effective treatment strategy for patients with KRASG12C tumors.

Significance:

Resistance to KRASG12C inhibitors is a growing clinical concern. The synergistic interaction observed between azenosertib and multiple KRASG12C inhibitors could result in deeper and more durable responses.
Non-small cell lung cancer treated with epidermal growth factor receptor inhibitors: the effect of concurrent medications on patient outcomes
Authors: Manninen Otto , Iivanainen Sanna , Arffman Martti , Koivunen Jussi Pekka
Published: January 2025

Introduction: EGFR tyrosine kinase inhibitor (TKI)-induced rash can be alleviated with tetracyclines (TCN) and topical corticosteroids (TCS), whereas drugs for acid-related disorders (DARD) can affect EGFR TKI absorption. The present study investigated the concomitant use of TCNs, TCSs, and DARDs with EGFR-TKIs in non-small cell lung cancer (NSCLC) and whether these affect patient outcomes.
Methods: We retrospectively collected data from all patients (n=1498) who had purchased for EGFR TKIs (erlotinib, gefitinib, and afatinib) in Finland between 2011-2020. Overall survival (OS) and time on treatment (ToT) were analyzed from the first EGFR TKI purchase.
Results: Early TCN purchases were registered in 298 (19.6%) patients; early TCS and DARD purchases were observed in 154 (10.1%) and 192 (12.9%) while similar percentages were detected in the EGFR mutant cohort. In the entire cohort, early purchase of TCSs and TCNs was associated with improved ToT, OS, and DARDs with inferior outcomes. In the multivariate analysis, TCSs retained their significance in ToT (HR, 0.78; 95% 0.66-0.94), TCNs in OS (HR, 0.73; 95% 0.63-0.84), and DARDs in both (HR, 1.28; 95% 1.091-1.495; HR, 1.19; 95% 1.01-1.41). In the EGFR mutant cohort, similar non-significant trends were observed for TCSs and DARDs. In the analysis according to EGFR TKI, erlotinib users had improved outcomes when early TCN or TCS purchases were registered, whereas DARDs were associated with worse outcomes among gefitinib users.
Conclusions: Among EGFR-TKI-treated NSCLCs, the use of TCN, TCS, and DARD can affect treatment outcomes that should be considered in optimal patient care.
Posterior nasal nerve neurolysis in addition to radiofrequency ablation of the inferior turbinates for patients with chronic rhinitis
Authors: Huang Chien-Yu , Liao Jyun-Yi , Teng Han-Lo , Kang Bor-Hwang , Lin Yaoh-Shiang , Hsieh Jun-Wei
Published: January 2025

Introduction: This study aimed to evaluate the outcome of radiofrequency ablation of the inferior turbinates (RFIT) combined with posterior nasal nerve neurolysis (RPN3) in comparison with RFIT alone in the treatment of patients with chronic rhinitis unresponsive to pharmacological therapy.

Methods: A retrospective cohort study was conducted on adult and adolescent patients with chronic rhinitis who demonstrated a poor response to medication. Patients with a total 24-hour reflective total nasal symptom score (rTNSS) of ≧5, rhinorrhea score of ≧2, and congestion score of ≧2 were included. The treatment outcomes of patients who underwent RPN3 and RFIT alone were assessed. The primary endpoint was the change from baseline in 12-h reflective total nasal symptom score (rTNSS), nasal obstruction symptom evaluation scores (NOSE), and the response rate defined as rTNSS improved ≧by 30% during follow-ups.

Results: A total of 64 patients were included (45 males, 70.3%). Overall, 49 patients underwent RPN3, and 15 patients underwent RFIT alone. The rTNSS had improved by 78.4% and 65.8% in RPN3 and RFIT groups, respectively (both p < 0.001). The NOSE score had improved by 92.89% and 86.81% in the RPN3 and RFIT groups (both p < 0.001), respectively. Patients in the RPN3 group demonstrated statistically significantly better results after three months than patients in the RFIT alone group (p < 0.05). The response rate was 98% in the RPN3 group after 3 months.

Conclusions: The proposed RPN3 alleviated rhinitis symptoms, which demonstrated a high response rate with a superior symptom control rate than RFIT alone in chronic rhinitis with severe rhinorrhea and nasal congestion cases.
O papel do destinador transcendente nos acontecimentos
Authors: Tatit Luiz
Published: January 2025

Throughout this paper, we propose a more accurate reflection on the Addresser function, extending it from the narrative universe to recent studies of unexpected events. Our starting point is the fact that the same phenomenon can be considered impactful for some and indifferent, or even non-existent, for others. Just as the narrative subject recognizes their object of pursuit by the values that accentuate and set it apart from other objects in the world, this “valuation” being the result of the persuasive actions of a trustworthy addresser, the subject struck by the so-called unexpected event can only distinguish it as such if they are able to glimpse in its core individual values, or parts of them, that have already been transmitted to them by one of their addressers sometime in their lives. In fact, the entire event presents itself as an unprecedented arrangement of these values apprehended in isolation by the subject, an arrangement that tends to be deciphered later on, in the transition from the affective impact to its intellectual resolution. It is within this interval that the subject shows astonishment. In the absence of an addresser capable of preparing them to identify these pertinent values and even to equip them with unknown (or transcendent) values, we would not have any event at all.
A cólera e suas oscilações tensivas
Authors: Beividas Waldir
Published: January 2025

In this text, I present two approaches. In the first, I briefly visit three authors who inaugurated what today constitutes the so-called tensive semiotics: A. J. Greimas, B. Pottier and Cl. Zilberberg. In this first movement, I seek to expose the pioneering reflections of these authors on the concept of tensivity, intensity and gradualness, key concepts that will be the methodological basis of the construction of tensive semiotics, in its current models of analysis. I also extend the exposition and visit the reflection of two Brazilian authors, who have explored operational pathways of Pottier's sinusoidal model to extract from it, on the one hand, a flexibilization in the treatment of the epistemic field of Greimassian semiotics (I. C. Lopes) as well as, on the other, a dynamization in the approach of passions, of veridiction, and their application in the analysis of the semiotics of song (R. Mancini). In the second movement I present my own catenary model, inspired by Zilberberg's inaugural reflections on tensivity, and I carry out a brief analysis that focuses on the tensive oscillations of the passion of anger, using Greimas' analysis of this passion as a parameter.
A “questão social” no intercâmbio cultural francês-alemão: Gans, Marx e a recepção de Saint-Simon
Authors: Bienenstock Myriam , Eichenberger Hernandez Vivan
Published: January 2025

O artigo reconstitui a recepção do sansimonismo na Alemanha. Para tanto, mostra como hegelianismo e sansimonismo foram inicialmente confundidos. Carové e Gans, contudo, buscaram desde logo marcar as diferenças entre ambos. No caso de Gans, porém, o problema da plebe, presente no interior do pensamento de Hegel, levou-o a reavaliar, positivamente, o sansimonismo e esboçar uma compreensão autônoma do problema da pobreza. A leitura de Gans é caracterizada em contraste com a de Marx.
The Insurance Value of Financial Aid
Authors: Fan Kristy , Fisher Tyler J. , Samwick Andrew A.
Published: January 2025

Prior studies of means-testing in college financial aid formulas have analyzed the disincentives to save attributable to the inclusion of assets in the formulas. Such disincentives are only half of a standard incentives-insurance tradeoff. When income is uncertain, a financial aid formula that conditions aid on assets and income provides insurance against that uncertainty. Using a stochastic, life-cycle model of consumption and labor supply, we show that the insurance value of financial aid is substantial. Compensating families for the loss of the income- and asset-contingent elements of the current formula requires additional aid sufficient to reduce the net cost of attendance by 11 to 22 percent. This compensating variation is net of the negative welfare conse- quences of the disincentives to work and save inherent in the means-testing of financial aid. Replacing just the financial aid tax on assets with a lump sum also reduces welfare.
Gaps That Do Not Sprout
Authors: Orth Wesley , Yoshida Masaya
Published: January 2025

This squib investigates a prohibition on sprouted remnants in cases of verbal Gapping with an implicit argument in the antecedent. We explore both ellipsis derivations and Across-The-Board-movement derivations for the Gapping structure to determine the underlying cause of this restriction. We find that the ellipsis derivations of verbal Gapping do not block the presence of a sprouted remnant or predict differences in the acceptability of sprouted remnants in verbal Gapping and Pseudogapping. On the other hand, we show that the restriction against sprouting in verbal Gapping constructions is captured as a consequence of issues faced in trace-binding in Across-The-Board-movement.
How open are hybrid journals included in transformative agreements?
Authors: Jahn Najko
Published: January 2025

The ongoing controversy surrounding transformative agreements, which aim to transition subscription-based journal publishing to full open access, highlights the need for large-scale studies assessing the impact of these agreements on hybrid open access. By combining multiple open data sources, including cOAlition S Journal Checker, Crossref, and OpenAlex, this study presents a novel approach that analyzes over 700 agreements. Results suggest a strong growth in open access, from 4.3% in 2018 to 15% in 2022. Over five years, 11,189 hybrid journals provided open access to 742,369 out of 8,146,958 articles (9.1%). Authors who could make use of transformative agreements contributed 328,957 open access articles (44%) during this period, reaching a peak in 2022 with 143,615 out of 249,511 open access articles (58%). While this trend was predominantly driven by the three commercial publishers Elsevier, Springer Nature, and Wiley, open access uptake varied substantially across journals, publishers, disciplines, and countries. In particular, the OECD and BRICS areas revealed different publication trends. In conclusion, this study suggests that current levels of implementation of transformative agreements are insufficient to bring about a large-scale transition to full open access.
Ukrainian Visions of Peace: (Re-)Shaping Peace through Victory
Authors: Kyselova Tetiana , Landau Dana M.
Published: January 2025

How can peace be achieved in Ukraine following Russia’s full-scale invasion of February 2022? In contrast to the impulse of many in the field of peacebuilding to call for concessions through a negotiated settlement, Ukrainian voices have consistently called for support of its military self-defense to achieve peace through victory. Heeding the peacebuilding field’s stated commitment to the principle of local ownership, by which those affected by war should take the lead in the pursuit of peace, this article analyzes Ukrainian articulations of peace at the governmental, civil society, and grassroots levels since 2022. We find that Ukrainians view peace primarily through the lens of victory. Taking these Ukrainian visions of peace seriously, we discuss potential tensions and challenges contained in the notion of peace through victory, including tensions between peace by armed resistance and peace by peaceful means, between the goals of Ukrainian victory and defeat of Russian imperialism, between peace and justice, as well as between militarization and democracy. The article concludes with a call for deeper scholarly and practitioner engagement with Ukrainian conceptions of peace through victory.
A Cross-country Study of COVID-19 Mortality Rate: How Do Institutions Make a Change?
Authors: Tang Chor Foon , Fakih Ali , Abosedra Salah
Published: January 2025

The role of institutions and other major factors in explaining the global behaviour of COVID-19 mortality rate is investigated by utilising cross-sectional data of 124 countries. Results obtained support the view that countries with higher economic growth, higher health quality and larger size of the elderly population are more likely to have a higher rate of mortality caused by COVID-19. Furthermore, negative relationships between education, institutions and mortality rate are found. These results extend recent findings on the global behaviour of COVID-19 mortality rate by highlighting the importance of the quality of a country’s institutions, which is lacking in previous research. The article offers some recommendations based on the reported results.
Triage body temperature predicts outcome in cats at emergency department admission: a retrospective study of 1440 cases (January 2018 to December 2021)
Authors: Pontiero Alessandra , Bulgarelli Cecilia , Ciuffoli Elena , Buzzurra Francesca , Villani Agnese , Troìa Roberta , Giunti Massimo
Published: January 2025

Objectives

The aim of the study was to evaluate the association between triage body temperature (BT) and outcome in cats presenting to the emergency department (ED).

Methods

A retrospective observational study was conducted on cats presented to the ED. BT, clinical diagnosis and outcome were recorded. BT was categorised as follows: normothermia (37.8–39.7°C); hyperthermia (⩾39.8°C); mild hypothermia (36.8–37.7°C); moderate hypothermia (35.6–36.7°C); severe hypothermia (33.1–35.5°C); and critical hypothermia (⩽33°C). Outcome in the ED was categorised as death, euthanasia, hospital admission and discharge. Outcome at hospital discharge was evaluated in patients admitted to the intensive care unit (ICU). Systemic inflammatory response syndrome (SIRS) was identified in patients. No-SIRS cats were divided into three disease categories (urinary system, cardiovascular and miscellanea) and SIRS cats into four categories (urinary system, cardiovascular, trauma and miscellanea). The presence of sepsis was evaluated. Non-parametric statistics were used.

Results

A total of 1440 cats were included. The hospital mortality rate was 21.9%. Hypothermia in the ED was reported in 510 (35.4%) cats, normothermia in 849 (59%) cats and hyperthermia in 81 (5.6%) cats. In the ED, the median temperature in non-survivors (35.4°C, 95% confidence interval [CI] 34.6–36.3) was significantly lower than in survivors (38.2°C, 95% CI 38.1–38.3; P <0.0001). The risk of non-survival in the ED was significantly higher in cats with a decreased BT, progressively increasing with the severity of hypothermia ( P <0.0001). Furthermore, BT was significantly associated with a higher risk of mortality in the ICU ( P <0.0001). A diagnosis of sepsis was associated with a high prevalence of hypothermia (79/124 cats, 63.7%) and a higher risk of non-survival (odds ratio [OR] 2.62, 95% CI 1.52–4.54; P = 0.0006). The mortality risk significantly increased in SIRS cats with a cardiovascular disease (OR 8.27, 95% CI 4.09–16.68; P <0.0001).

Conclusions and relevance

Hypothermia is common in cats at ED admission and is significantly associated with outcome. Triage hypothermia might identify patients with sepsis or SIRS complicated by comorbidities, such as cardiovascular and urinary diseases.
Active cycle of breathing technique versus oscillating positive expiratory pressure therapy: Effect on lung function in children with primary ciliary dyskinesia; A feasibility study
Authors: Fashho Bishara , Rumman Nisreen , Lucas Jane , Halaweh Hadeel
Published: January 2025

Background: Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder requiring airway clearance techniques for mucus removal. We aimed to evaluate the feasibility and the effect of the active cycle of breathing technique (ACBT) versus oscillating positive expiratory pressure therapy (OPEP) in improving lung function and functional exercise capacity among children with PCD in Palestine. Methods: 32 PCD children (6–18 years) were included in a 12-week home-based feasibility study. They were assigned randomly into two groups: ACBT and OPEP. Data collection included spirometry measurements, and the six-minute walk test (6MWT). Results: After 12 weeks of regular airway clearance techniques (ACT), the FEV1, MEF25-75%, and the 6MWT demonstrated statistically significant differences ( p = .02, p = .04, and p = .05 respectively) between the two groups, in favor of the OPEP group with the effect size of Cohen’s d (0.86, 0.76, and 0.71) respectively. However, there was no significant difference ( p > .05) between the two groups in FVC and FEV1/FVC. Additionally, only in the OPEP group, significant differences were recorded between pre and post-tests for FEV1 and 6MWT ( p < .05). Conclusion: The randomized study design comparing ACBT and OPEP was feasible and acceptable to patients. OPEP demonstrates potential for managing respiratory health; however, treatments should be individualized to address each patient’s specific needs. Further research with larger cohorts is needed to assess the effectiveness of both methods.