bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of prognostic nutritional index on mortality among patients receiving coronary artery bypass grafting surgery: a retrospective cohort study
Authors: Sun Lin , Liu Zihua , Cui Xueying , Hu Bo , Li Wei , Pan Yilin , Sun Yangyang , Wang Zikun , Dong Wanyue , Xu Kai , Han Lixiang , Zhang Yangyang , Zhao Xin , Li Zhi
Published: February 2025

Background

The Prognostic Nutritional Index (PNI), calculated from serum albumin levels and lymphocyte counts, is a simple and objective measure of nutritional status. While PNI has been shown to be a significant prognostic tool in gastrointestinal surgery and heart failure, its role in patients undergoing coronary artery bypass grafting (CABG) remains unclear. This study aims to evaluate whether PNI can serve as a meaningful risk factor for patients undergoing CABG.

Methods

This observational retrospective analysis involved a substantial sample of 2889 patients who underwent isolated CABG at one of four medical centres. The primary outcomes included short- and long-term mortality. Perioperative serum albumin levels and total lymphocyte counts used to calculate PNIs were collected 48 hours before the operation, 24 hours after the operation and at discharge. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors of short-term mortality. Survival and relative risks were assessed using Cox regression analysis and the Kaplan-Meier test.

Results

Among the 2889 patients, 64 (2.2%) died within 30 days following CABG. Multivariate logistic regression revealed that higher preoperative PNI was independently associated with reduced short-term mortality (OR=0.852 per unit increase, 95% CI 0.802 to 0.904, p<0.001). Regarding long-term outcomes, among the 2825 patients who were discharged alive, 199 deaths occurred over a median follow-up period of 54.9 months. Patients with a normal PNI at discharge (>40) exhibited significantly higher long-term survival rates compared with those with a lower PNI (≤40) (log-rank p=0.003). Multivariate Cox regression analysis confirmed that a normal PNI at discharge(>40) independently predicted a lower risk of long-term all-cause mortality (HR=0.718, 95% CI 0.529 to 0.974, p=0.033).

Conclusions

PNI at various time points may play a crucial predictive role in mortality among CABG-treated patients, and a low PNI serves as a risk factor for both short- and long-term survival.
Concussion history and knowledge among top-level youth karate athletes
Authors: Augustovicova Dusana Cierna , Arriaza Rafael , Lystad Reidar P
Published: February 2025

Objective

To examine concussion experiences and knowledge among top-level youth karate athletes.

Methods

This cross-sectional study collected data during the 12th World Karate Championships for cadets, juniors and under-21 athletes (held in Konya, Turkey, 2022). All 1414 registered athletes from 95 countries were invited to complete a 16-item paper-based questionnaire assessing demographic data, concussion history and concussion knowledge prior to the competing at the tournament. χ2and Fisher’s exact tests were used to analyse differences by sex, age group and continental karate federation.

Results

A total of 654 athletes (46.3% response rate), including 286 (43.7%) females and 368 (56.3%) males, participated in the study, with 29.9% reporting one or more concussions during participation in karate training or competition. Older age groups (under 21 years) reported significantly higher concussion rates than younger athletes (56.9% vs 31.1% juniors and 24.7% cadets; p<0.001). Concussion knowledge revealed considerable gaps, with only 24.5% of athletes correctly identifying a concussion and 68.9% believing loss of consciousness was required for a concussion diagnosis. Misconceptions varied significantly across geographical regions, with Asian and African athletes demonstrating the greatest need for targeted education. Female athletes demonstrated better concussion reporting attitudes than males (60.4% vs 48.9%, p=0.004).

Conclusions

This study highlights the prevalence of concussions and significant knowledge gaps among top-level youth karate athletes, emphasising the need for tailored educational interventions to improve concussion recognition and management within the karate community.
Pooled screening for CAR function identifies novel IL-13Rα2-targeted CARs for treatment of glioblastoma
Authors: Gordon Khloe S , Perez Caleb R , Garmilla Andrea , Lam Maxine S Y , Aw Joey J Y , Datta Anisha , Lauffenburger Douglas A , Pavesi Andrea , Birnbaum Michael E
Published: February 2025

Background

Chimeric antigen receptor (CAR) therapies have demonstrated potent efficacy in treating B-cell malignancies, but have yet to meaningfully translate to solid tumors. Nonetheless, they are of particular interest for the treatment of glioblastoma, which is an aggressive form of brain cancer with few effective therapeutic options, due to their ability to cross the highly selective blood-brain barrier.

Methods

Here, we use our pooled screening platform, CARPOOL, to expedite the discovery of CARs with antitumor functions necessary for solid tumor efficacy. We performed selections in primary human T cells expressing a library of 1.3×106third generation CARs targeting IL-13Rα2, a cancer testis antigen commonly expressed in glioblastoma. Selections were performed for cytotoxicity, proliferation, memory formation, and persistence on repeated antigen challenge.

Results

Each enriched CAR robustly produced the phenotype for which it was selected, and one enriched CAR triggered potent cytotoxicity and long-term proliferation on in vitro tumor rechallenge. It also showed significantly improved persistence and comparable tumor control in a microphysiological human in vitro model and a xenograft model of human glioblastoma, but also demonstrated increased off-target recognition of IL-13Rα1.

Conclusion

Taken together, this work demonstrates the utility of extending CARPOOL to diseases beyond hematological malignancies and represents the largest exploration of signaling combinations in human primary cells to date.
Primary neuraxial anesthetic for elective total knee arthroplasty in patient with left ventricular assist device
Authors: Sheikh Hanin , Klein Julia Isabella , Higgins III Kenneth Elliott , Patton John W , Chu Benjamin
Published: February 2025

Background

There is a rising number of patients with left ventricular assist devices (LVADs) undergoing non-cardiac procedures, both emergent and elective. Historically, anesthetic options for these patients have been limited to general anesthesia. Limited data exists for the use of neuraxial anesthesia in patients with LVADs despite its common use in orthopedic procedures for non-LVAD patients. Given the benefits of neuraxial anesthesia and the rising population of LVAD patients undergoing elective procedures, a better understanding of LVAD patients’ candidacy for neuraxial anesthesia needs further investigation.

Case presentation

We report the case of a patient with an LVAD who successfully underwent a total knee arthroplasty with neuraxial anesthesia at a tertiary academic center. Preoperative transthoracic echo demonstrated stable cardiac function and an ejection fraction of 10–15% with a HeartMate 3 LVAD. The primary anesthetic was a lumbar epidural that was slowly titrated to a surgical anesthetic level and an adductor canal peripheral nerve catheter was placed preoperatively for postoperative analgesia. The patient remained hemodynamically stable throughout the case, with a perfusionist monitoring the LVAD’s function intraoperatively, and tolerated the anesthetic well. His postoperative course was uneventful.

Conclusion

Patients with LVADs should be considered candidates for neuraxial anesthesia with appropriate preoperative planning and perioperative management.
Performance of Sustainable Drainage Capillary Barrier Systems for Climate Change Adaptation in Temperate Climates
Authors: Holmes Jessica Lauren , Stirling Ross , Taggart Richard , Thaman Narryn , Davie Colin T. , Glendinning Stephanie
Published: February 2025

Capillary Barrier Systems (CBS) offer a sustainable solution supporting Sustainable Drainage Systems (SuDS) to urban flooding: The occurrence of flooding in urban areas is increasing in response to more intense precipitation, changes in land use that increase runoff (e.g., reduction of green spaces), and reduced water retention of soils. The need for adaptation to the impacts of extreme weather extends to buried assets (e.g., utilities, pavement subbases and foundations) that are vulnerable to deterioration due to shrink-swell behaviour. Combined Sustainable Drainage Systems and capillary barriers, offer a solution to these challenges. Here, small-scale (110 mm diameter, 1 m length) column experiments are used to test capillary barrier systems, also modelled in HYDRUS 1-D, to consider the impact of relative grain size between the two constituent materials, the use of geosynthetic filter fabrics, and the thickness of the water retention layer on combined SuDS CBS performance under a range of storm inflows. Recycled materials including crushed concrete and water treatment residual (a waste product of the water treatment industry) are shown to be effective for use in SuDS-CBS. Laboratory experiments and numerical modelling demonstrate the importance of antecedent moisture conditions for determining the performance of a SuDS-CBS during rainstorm events.
Effect of modifying energy to protein ratio of alfalfa on ruminal fermentation, nitrogen use, methane production, and microbial composition in vitro
Authors: Poulin A. A. , Charbonneau Edith , Petri Renee M. , Thériault Mireille , Ouellet Daniel , Tremblay Gaëtan , Claessens Annie , Bertrand Annick , Hassanat Fadi
Published: February 2025

Effects of contrasted energy to protein ratios in alfalfa on in vitro rumen degradation characteristics and microbial composition were evaluated. Thirty-six alfalfa forages categorized as either superior (2.0) non-fiber carbohydrates (NFC) to crude protein (CP) ratio (NFC/CP; Ratio +; n = 18) or inferior (0.9) NFC/CP ratio (Ratio –; n = 18) were compared using a batch-culture in vitro technique. Forages were similar in their neutral detergent fiber concentrations (340 g/kg). Statistical analysis model considered treatment (Ratio + and Ratio –) as fixed effect while incubation run was a random effect, with significant treatment effect declared at P ≤ 0.05. After 24 h of incubation, apparent degradability of dry matter (DM; 57 vs. 53%), total gas production (263 vs. 228 mL) and total volatile fatty acids concentration (VFA; 48 vs. 42 mM) in ruminal fluid were greater for Ratio + than Ratio – alfalfa. Microbial N use efficiency (69 vs. 56 g of microbial N/100 g of N incubated) was greater with Ratio + than Ratio –, which was associated with an increase in ammonia-utilizing bacteria in the Ratio +. This work highlights the potential to reduce the environmental footprint of ruminants through forage management and plant breeding.
RESISTANCE GENES AGAINST YELLOW RUST PATHOGEN IN TRITICUM SPELTA: A POSSIBLE NEW Yr RESISTANCE GENE IN ACCESSION IARI276 AND Yr5 PRESENCE CONFIRMED IN PI348764
Authors: Arya Lovely , Shal Malavika N , Niranjana M , Jha SK , Patial Madhu , Saharan MS , Mallick Niharika , Raghunandan K , Priyanka A , Walia DP , Tomar Shiv Mangal Singh , Vinod .
Published: February 2025

Yellow/stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a major biotic stress in global wheat production. Introgression lines derived from the Triticum spelta accessions PI348764 and IARI276 showed high levels of yellow rust resistance at seedling and adult plant stage. The Yr5 gene located on 2B chromosome was previously the only stripe rust resistance gene described in T. spelta gene pool. By genotyping parental and introgressed material with markers linked with the Yr5 gene, we demonstrate that PI348764 likely carries Yr5, and that it appears to be absent from IARI276. By employing a combination of methods, including screening for adult plant resistance and seedling resistance at multiple field trials; bulked segregant analysis (BSA) on F5 families, and genotyping using wheat Breeders' 35K array; we show that YrIARI276 is a novel stripe rust resistance gene with putative chromosomal locations on 1BL, 1DL, 5AL or 7BL. Furthermore, genetic analysis revealed that YrIARI276 showed a goodness of fit to Mendelian ratios for a single dominant gene. As the gene is distinct from Yr5 and the chromosomal location is unique from earlier reported Yr genes, it will be useful in improving diversity of Yr gene repertoire in disease resistance breeding programmes.
Attention-based Fusion for Stroke Lesion Segmentation on Computed Tomography Perfusion Data
Authors: Sri Pothu Raju Chintha , Laskar Rabul Hussain , Ali Zulfiqar , Muhammad Ghulam
Published: February 2025

In recent times, stroke has emerged as a significant threat to humans, transforming affected brain tissue into core and penumbra regions. As the penumbra becomes irreversible over time, early core region segmentation is crucial. Automatic segmentation systems offer an efficient alternative to manual segmentation and aid radiologists in stroke lesion segmentation using Computed Tomography and Computed Tomography Perfusion (CTP) maps that comprise four parameter maps. This automatic segmentation is increasingly used in interactive, multimedia-based systems for diagnostic tools and AI-driven health applications. Top-performing models that follow the patch processing approach suffer from high inference times. To incorporate effective feature extraction at image-level inferences, which reduces the inference time, we present a hybrid fusion technique that combines early and bottleneck fusion, leveraging two separate encoders for effective feature extraction. Moreover, fusing the information from various fusion methods arbitrarily may not yield optimal results. Consequently, we have introduced two attention modules, i.e., cross-modal attention and cross-fusion attention modules, designed for the effective integration of features derived from diverse modalities and multiple fusion strategies, respectively. The findings highlight a considerable reduction in computational time alongside achieving a comparable dice score. Additionally, the incorporation of hybrid fusion and attention modules in the baseline notably increased the dice score from 0.482 to 0.521 in the validation dataset and achieved 0.48 in the test dataset of ISLES 2018. It also demonstrates competitive performance compared to existing models while maintaining efficient prediction times.
Supporting Large-Scale Distributed Simulations Through the Topic-Based Data Distribution Management System
Authors: Falcone Alberto , Garro Alfredo
Published: February 2025

Modeling and Simulation (M&S) is a fundamental technology to design and study complex systems in various industrial and scientific domains when real-world testing is impractical due to costs, safety concerns, and time constraints. To promote the reusability and interoperability of simulation entities, allowing them to interoperate without geographic barriers, distributed simulation has been introduced. One of the most widely adopted standards for distributed simulation is the IEEE 1516-2010 - High Level Architecture (HLA). Among the services provided by HLA, a key one is the Data Distribution Management (DDM) which allows to reduce the transmission and reception of unnecessary data in order to improve communication effectiveness among simulation entities. This is done by computing the so-called “region matching”, i.e., the overlap between “update” and “subscription” regions. In this paper, a novel DDM system called
Topic-based publish-subscribe Messaging System (TBMS)
is proposed to improve the performance, reliability, and scalability of DDM services. Unlike traditional algorithms, this system revolves around the concept of “topic” that favors a contextualized approach to the match, avoiding the filtering of the information actually of interest on the receiver side. Experiments have been conducted to evaluate the proposed TBMS in terms of utilization and waiting time metrics.
Introducing SIGCSE Virtual
Authors: Dorodchi Mohsen , Gal-Ezer Judith , Cooper Stephen
Published: February 2025

SIGCSE Virtual 2024, the First ACM Virtual Global Computing Education Conference, will be held fully online from December 5 to 8, 2024. The conference has different themes based on the global aspects of CS education, while considering regional circumstances, and the sessions are offered considering time-zone constraints.
ITiCSE 2024 Recap
Authors: Lonati Violetta , Monga Mattia , Barendsen Erik
Published: February 2025

The 29th annual ACM conference on Innovation and Technology in Computer Science Education (ITiCSE) was held in Milan, Italy, July 5-10, 2024. Despite some last-minute changes due to an ongoing student protest at the University of Milan, we can consider this edition a success. A total of 345 participants attended ITiCSE, coming from 36 different countries
SIGCSE Technical Symposium 2025: Leading the Transformation
Authors: Stone Jeffrey A. , Yuen Timothy
Published: February 2025

The 2025 SIGCSE Technical Symposium will take place in Pittsburgh, Pennsylvania, from February 26 to March 01, 2025. The SIGCSE community will gather at the David L. Lawrence Convention Center on the banks of the Allegheny River. Our theme for this year is "Leading the Transformation," reflecting the role of the computer science education community in adapting educational practice to new technologies and challenges.
T@Member Spotlight: Bruce Scharlau
Authors: Smith Julie M. , Wallace Charles , Scharlau Bruce
Published: February 2025

Dr. Scharlau is an Emeritus Senior Lecturer in the Department of Computing Science at the University of Aberdeen, UK.
Report on LiCS 2024
Authors: Sobociński Paweł
Published: February 2025

LiCS 2024 was held 8--11 July in Tallinn, collocated with ICALP 2024 and FSCD 2024 as well as 14 workshops. The combined number attendees was almost 500. The number of registrations for LiCS specifically was over 120, with around 30 additional participants who chose an the all inclusive package and participated in several of the conferences and workshops.
Report on WiL 2024
Authors: Nantes-Sobrinho Daniele , Pimentel Elaine , Prince Tephilla
Published: February 2025

The Women in Logic Workshop (WiL) aims to increase awareness of the valuable contributions made by women in logic. Its primary goal is to promote excellent research led by women, ultimately increasing their visibility and representation within the community.
Drifting and Evolving: The graph-based Genetic Programming community has entered a new Era
Authors: Kalkreuth Roman
Published: February 2025

It's now over two years since Julian F. Miller sadly passed away in February 2022 and lots of development has taken place within the graph-based genetic programming (GGP) community since then.
The October 2024 Issue
Authors: Uhlig Steve
Published: February 2025

This October 2024 issue contains three technical papers, one of which is of a rather educational nature and can be considered both an educational contribution and a technical paper.
Principal Branches of Inverse Trigonometric and Inverse Hyperbolic Functions
Authors: Dempsey Kevin M.
Published: February 2025

We discuss principal branches for five square root functions and for the inverse trigonometric and inverse hyperbolic functions. We take the standard reference in this area to be the NIST Digital Library of Mathematical Functions (DLMF). We adopt the notation for and the definitions of the principal branches of the inverse functions in the DLMF. Similarly, the branch cuts for the inverse functions are defined as per the DLMF. Our goal is to use complex analysis to turn the definitions of the principal branches in the DLMF into concrete expressions that hold on the entirety of their respective cut planes. The square root principal branch expressions are new breakthrough discoveries that lead smoothly to four of the concrete expressions. We expand the number of concrete expressions in Sections 4.23 and 4.37 in the DLMF from two to eight. Three of these eight concrete expressions were in print in 1924. One of the latter is still awaiting inclusion in the DLMF. Taken altogether, we provide a computationally efficient resource for computer algebra in programming languages, specifically for the principal branches of the inverse trigonometric and inverse hyperbolic functions.
Rectangular Hardinian Arrays
Authors: Dougherty-Bliss Robert , Spahn George
Published: February 2025

We resolve some open conjectures from the OEIS about Hardinian arrays (see A253217). In particular, we show via the transfer matrix method that

H
r

(
n, k
), the number of
n × k
Hardinian arrays with parameter
r
is a polynomial in
n
of degree
r
when
r
and
k
are fixed and
n
is sufficiently large. Our implementation of the main result in Maple and Python involves computing with large, sparse matrices, both numeric and symbolic.
Towards Learning the Positive Real Discriminant of the Wnt Signaling Pathway Shuttle Model
Authors: Englander Aviva K. , Rodriguez Jose Israel
Published: February 2025

We use machine learning to approximate the space of steady states in the shuttle model for the Wnt Signaling Pathway. In this ongoing work, we combine these methods with computational algebra to investigate a question by Gross, Harrington, Rosen, and Sturmfels.
New ACM Open Publishing Policy
Authors: Duran Rodrigo Silva
Published: February 2025

In June 2020, the ACM Council voted to transition ACM's Publications program to a 100% sustainable Open Access model within 5 years with the ultimate goal of making all ACM-published articles open access upon publication. This deadline is fast approaching, and for some ACM-published conference articles the new model is already active. ACM is revamping its publication model with its new ACM OPEN policy. ACM has discussed the potential benefits (open articles are downloaded 100-150% more and cited 70% more frequently) and the challenges of this model in depth. Instead of discussing the merits of the model, we would like to present to our community in concrete terms the impacts of this new publication model for authors: What will change when I publish in a SIGCSE-related conference from 2025 onwards when ACM transitions to a 100% Open Access publication model?
SIGCSE Technical Symposium 2025: Information for Attendees
Authors: Stone Jeffrey A. , Yuen Timothy , Rebelsky Samuel A. , Shoop Libby , Prather James
Published: February 2025

The 2025 SIGCSE Technical Symposium will soon be upon us! The Technical Symposium will take place in Pittsburgh, Pennsylvania from February 26 to March 01, 2025. We are looking forward to welcoming the SIGCSE community at the David L. Lawrence Convention Center on the banks of the Allegheny River. Our theme for this year is "Leading the Transformation."
Member Spotlight: Samuel Mann
Authors: Smith Julie M. , Wallace Charles , Mann Samuel
Published: February 2025

Dr. Samuel Mann is a Professor at Otago Polytechnic in Dunedin, New Zealand, focused on computing and sustainability. He was a leader in developing the ACM's draft statement on Education for Sustainability.
Mechanics of Single Cytoskeletal Filaments
Authors: Romet-Lemonne Guillaume , Leduc Cécile , Jégou Antoine , Wioland Hugo
Published: February 2025

The cytoskeleton comprises networks of different biopolymers, which serve various cellular functions. To accomplish these tasks, their mechanical properties are of particular importance. Understanding them requires detailed knowledge of the mechanical properties of the individual filaments that make up these networks, in particular, microtubules, actin filaments, and intermediate filaments. Far from being homogeneous beams, cytoskeletal filaments have complex mechanical properties, which are directly related to the specific structural arrangement of their subunits. They are also versatile, as the filaments’ mechanics and biochemistry are tightly coupled, and their properties can vary with the cellular context. In this review, we summarize decades of research on cytoskeletal filament mechanics, highlighting their most salient features and discussing recent insights from this active field of research.
Kinetics of Amyloid Oligomer Formation
Authors: Wei Jiapeng , Meisl Georg , Dear Alexander J. , Michaels Thomas C.T. , Knowles Tuomas P.J.
Published: February 2025

Low-molecular-weight oligomers formed from amyloidogenic peptides and proteins have been identified as key cytotoxins across a range of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Developing therapeutic strategies that target oligomers is therefore emerging as a promising approach for combating protein misfolding diseases. As such, there is a great need to understand the fundamental properties, dynamics, and mechanisms associated with oligomer formation. In this review, we discuss how chemical kinetics provides a powerful tool for studying these systems. We review the chemical kinetics approach to determining the underlying molecular pathways of protein aggregation and discuss its applications to oligomer formation and dynamics. We discuss how this approach can reveal detailed mechanisms of primary and secondary oligomer formation, including the role of interfaces in these processes. We further use this framework to describe the processes of oligomer conversion and dissociation, and highlight the distinction between on-pathway and off-pathway oligomers. Furthermore, we showcase on the basis of experimental data the diversity of pathways leading to oligomer formation in various in vitro and in silico systems. Finally, using the lens of the chemical kinetics framework, we look at the current oligomer inhibitor strategies both in vitro and in vivo.
Youth with Behavioral Health Symptoms in the Juvenile Legal System: From Assessment of Needs to Interventions to Scalability
Authors: Kemp Kathleen , Sheerin Kaitlin , Pederson Casey , Grant Miyah , Modrowski Crosby , Spirito Anthony
Published: February 2025

This article provides an overview of the current state of assessment and clinical intervention approaches for youth with juvenile legal system (JLS) involvement. The review includes (a) a brief overview of characteristics of youth with JLS involvement; (b) current screening and assessment frameworks within the JLS that identify treatment needs; (c) an overview of effective clinical interventions for common behavioral health concerns among youth with JLS involvement, including information about tailoring interventions to address the multiple intersecting identities (e.g., race, ethnicity, gender identity, sexual orientation) of youth within the JLS; and (d) an overview of implementation models and scalability of interventions.
Immune Dysregulation in Obesity
Authors: Jiang Zewen , Tabuchi Chihiro , Gayer Sarah G. , Bapat Sagar P.
Published: February 2025

The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity—a state characterized by chronic inflammation and systemic dyshomeostasis—there is growing scientific and clinical interest in understanding how obesity reshapes immune function. In this review, we propose that obesity is not merely an altered metabolic state but also a fundamentally altered immunological state. We summarize key seminal and recent findings that elucidate how obesity influences immune function, spanning its classical role in microbial defense, its contribution to maladaptive inflammatory diseases such as asthma, and its impact on antitumor immunity. We also explore how obesity modulates immune function within tissue parenchyma, with a particular focus on the role of T cells in adipose tissue. Finally, we consider areas for future research, including investigation of the durable aspects of obesity on immunological function even after weight loss, such as those observed with glucagon-like peptide-1 (GLP-1) receptor agonist treatment. Altogether, this review emphasizes the critical role of systemic metabolism in shaping immune cell functions, with profound implications for tissue homeostasis across various physiological contexts.
Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms
Authors: Shaw Andrew A. , Steketee Jeffery D. , Bukiya Anna N. , Dopico Alex M.
Published: February 2025

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders. We examine (a) the physicochemical properties of toluene that allow this inhalant to primarily target the lipid-rich brain; (b) the cell types targeted by toluene (neurons, different types of glia), while considering a cerebrovascular component; and (c) putative molecular mechanisms by which toluene may modify receptor function while analyzing structural features that allow toluene to directly interact with membrane lipids or specific proteins. This information constitutes a stepping stone to design pharmacotherapies that counteract toluene brain intoxication.
Pharmacology of Intestinal Inflammation and Repair
Authors: Deraison Céline , Vergnolle Nathalie
Published: February 2025

Chronic inflammation is a common trait in the pathogenesis of several diseases of the gut, including inflammatory bowel disease and celiac disease. Control of the inflammatory response is crucial in these pathologies to avoid tissue destruction and loss of intestinal function. Over the last 50 years, the identification of the mechanisms and mediators involved in the acute phase of the inflammatory response, which is characterized by massive leukocyte recruitment, has led to a number of therapeutic options. New drugs targeting inflammatory flares are still under development. However, interest on the other end of the spectrum—the resolution and repair phases—has emerged, as promoting tissue functional repair may maintain remission and counteract the chronicity of the disease. This review aims to discuss the current and future pharmacological approaches to the treatment of chronic intestinal inflammation and the restoration of functional tissues.
Gadoxetic Acid–enhanced MRI Scoring Model to Predict Pathologic Features of Hepatocellular Carcinoma
Authors: Zhang Kun , He Kan , Zhang Lei , Li Wen-Cui , Xie Shuang-Shuang , Cui Ying-Zhu , Lin Li-Ying , Shen Zhi-Wei , Xia Shuang , Su Xiao-Min , Zhang Hui-Mao , Ye Zhao-Xiang , Shen Wen
Published: February 2025

A scoring model based on gadoxetic acid–enhanced MRI enabled noninvasive preoperative prediction of high-risk pathologic features in patients with hepatocellular carcinoma and could be used to predict early recurrence.
Preoperative Chest CT Myosteatosis Indicates Worse Postoperative Survival in Stage 0–IIB Non–Small Cell Lung Cancer
Authors: Mantz Lea , Mercaldo Nathaniel D. , Simon Judit , Kaess Philipp , Yang Kai , Dietrich Anna-Sophia W. , Tonnesen P. Erik , Troschel Amelie S. , Marquardt J. Peter , Sehi Daniel A. , Javidan Cylen , Chung Jonathan H. , Gaissert Henning A. , Ferguson Mark K. , Fintelmann Florian J.
Published: February 2025

Myosteatosis markers at preoperative chest CT were associated with worse survival after resection of stage 0–IIB non–small cell lung cancer, independent of the skeletal muscle index and subcutaneous adipose tissue.
Hormonal Regulation of Background Parenchymal Enhancement at Contrast-enhanced Mammography
Authors: Nissan Noam , Sevilimedu Varadan , Gluskin Jill , Arita Yuki , Keating Delia M. , D’Alessio Donna , Fruchtman-Brot Hila , Ochoa-Albiztegui R. Elena , Sung Janice S. , Jochelson Maxine S.
Published: February 2025

Background parenchymal enhancement observed at contrast-enhanced mammography decreased with menopause and use of tamoxifen and increased with lactation, hormone replacement therapy use, and tamoxifen cessation, suggesting these effects should be considered at imaging interpretation.
MRI and Surgical Findings Refine Concepts of Type 2 Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension
Authors: Lützen Niklas , Beck Jürgen , Carlton Jones Lalani , Fung Christian , Demerath Theo , Rau Alexander , Zander Charlotte , Wolf Katharina , Volz Florian , El Rahal Amir , Urbach Horst
Published: February 2025

Type 2 spinal cerebrospinal fluid leaks in patients with spontaneous intracranial hypotension occur after lateral dural tears through which the arachnoid herniates, which is visible on MRI scans (ie, the “bud-on-branch” sign).
Navigating What Is Not Known—Patients’ Experience of the Life Threat Connected to Allogeneic Stem Cell Transplantation
Authors: Reimer Alinda , Schepers Carolin , Ley Merle , Schoerger Berenike , Pralong Anne , Voltz Raymond , Holtick Udo , Herling Marco , Simon Steffen T.
Published: February 2025

Background: Allogeneic stem cell transplantation (allo‐SCT) represents a firmly established therapeutic option for patients facing (non‐)malignant haematological diseases. Despite its curative potential, however, this treatment is associated with substantial morbidity and mortality rates as well as a decreased quality of life. Given this context, a scientific void needs to be addressed: How do patients deal with the existential situation of being exposed to a life threat despite the curative potential of their treatment? This study aims to explore the patients’ experiences considering their life threat in the context of the allo‐SCT.

Methods: Qualitative semistructured, in‐depth interviews were conducted with patients treated by allo‐SCT over the course of transplantation (before, during or after hospitalization). Interview data were interpreted using category‐based qualitative content analysis.

Results: Seventeen interviews were conducted. Results revealed a strong focus on hope and avoidance of dealing with the life threat. At the same time, challenges due to the lack of alternative treatments and the uncertain course were highlighted. The data revealed that patients wished to receive support by healthcare professionals, their carers and their social environment in general. Beyond that, patients desired to obtain honest information within an open discussion about a realistic prognosis and risk of treatment and course of disease.

Conclusion: The findings emphasize an interplay between hope, avoidance and psychological distress in the face of the patients’ life threat. To assist allo‐SCT recipients in navigating their life threat during treatment, it is desirable to establish avenues that provide adequate support.

Trial Registration: German Registry of Clinical Trials: DRKS00027290
Research on Optimization of the Upper Particle Size Limit of Gangue in Slurry Backfill Based on Interference Settlement
Authors: Lv Wenyu , Song Tianqi , Wu Yongping , Gu Wenzhe , Qiu Fengqi , Xie Panshi , Pan Hao , Lyu Chao , Guo Kai , Zhou Xinxin
Published: February 2025

With the increasing demand for gangue disposal in China, gangue slurry filling technology, as a necessary technical means for harmless disposal of gangue under low interference conditions, has been widely promoted in Western China, Mongolia, and Shaanxi regions. In order to optimize the upper limit particle size of gangue slurry under interference settlement conditions to ensure the safety of pipeline transportation, the article systematically carried out the gangue slurry characteristics and static settlement test, studied the interference settlement conditions of gangue slurry in the suspension of coarse particles characteristics, and analysis of the gangue particles obtained by the settling speed of engineering verification. The results show that gangue slurry has coarser particles, complex components, and high solid content characteristics, and its static settlement characteristics cannot truly restore the flow state in the pipeline. The particle settling velocity is affected by the concentration of slurry, rheological parameters, gangue particle size, and gangue fine particles of the density of the suspension medium through the mechanical derivation method to obtain the gangue particle settling velocity calculation formula. Moreover, take indoor large‐scale tests and field applications for double verification, the upper limit of particle size of 3.00 mm under the condition of the maximum sinking speed of 1.092 × 10−6 m/s can realize the start with the material did not happen to plug the pipe accident, the field test of the neighboring grouting filling effect is good.
Theoretical Perspectives on Adolescent Internet Addiction: A Comprehensive Literature Review
Authors: Jin Yishan , Jiang Shan
Published: February 2025

The increasing reliance on the internet has intensified concerns about internet addiction, especially among adolescents. Previous studies have associated adolescent internet addiction with detrimental psychological conditions and deteriorating social bonds. Nonetheless, a comprehensive theoretical framework for understanding the development of adolescent internet addiction remains elusive, impeding the advancement of research focused on creating effective educational and intervention strategies. This study undertakes a systematic review of existing theories and models related to adolescent internet addiction, offering an integrated theoretical framework that aims to elucidate the underlying causes and mechanisms. Our proposed framework seeks to enhance the conceptual foundation for future research, thereby facilitating the development of targeted interventions.
Inhibitory Effects and Mechanisms of Water‐Soluble Chitosan/Curdlan Edible Composite Coating on Polygalacturonase and β‐Glucosidase
Authors: Liu Kunyu , Jing Ziyu , Li Jiasi , Chang Jiaqi , Wang Hesheng , Jia Silong , Yu Youwei , Zhang Shaoying
Published: February 2025

Postharvest fruits such as cherry tomato (Lycopersicon esculentum var. cerasiforme A. Gray) are prone to rot owing to the infection of pathogens, leading to great economic losses to farmers. To investigate the inhibitory effect and mechanism of polygalacturonase and β‐glucosidase activity in cherry tomatoes and pathogenic fungi such as Alternaria (Nees: Fr) and Botrytis cinerea, various analyses including molecular simulation, ultraviolet spectrum, fluorescence spectrum, circular binary chromatography, inhibition rate, and enzymatic activity test were studied. The results showed that composite coating of water‐soluble chitosan (CTS)/curdlan (CUR) significantly inhibited the activities of polygalacturonase and β‐glucosidase in cherry tomatoes, Alternaria (Nees: Fr), and Botrytis cinerea. In addition, composite coating induced changes in enzyme conformation leading to a decrease in the rate of cell wall degradation in cherry tomatoes. The composite membrane inhibited 85% of polygalacturonase and 88% of the polygalacturonase and the ASP ASN ARG PRO GLU GLN and TRP residue of the β‐glucosidase, thereby significantly inhibiting the decay of cherry tomatoes. In conclusion, the composite coating might inhibit the enzyme activity altering the enzyme structure, which showed promise as an effective method for fruit preservation.
Microbial Quality and Hygienic Safety of Avocado Fruit Juice Sold in Merawi Town, Amhara, Ethiopia
Authors: Tilahun Tadele , Kumera Bulti , Kibret Mulugeta
Published: February 2025

Fruit juices are nutritious beverages used by people of all ages around the world. The microbial quality and safety of juices are closely monitored in developed countries but not in many developing countries. The objective of the present study was to evaluate the microbial quality and hygienic safety of fresh avocado fruit juice in Merawi town. The study was conducted in Merawi town from February 2019 to May 2019. It included 16 workers from five avocado juice houses for hygienic practice assessments. A total of 30 avocado fruit juice samples were collected for laboratory analysis. The samples were immediately transported to Bahir Dar University, Microbiology Laboratory for microbial culture. The results of the study were analyzed using descriptive statistics such as frequency, percentage, mean, and standard deviation. One‐way ANOVA was used to compare microbial mean counts. Out of all the participants in the survey, 93.75% were females, while the remaining 6.25% were males. All juice vendors (100% of participants) reported that they had not received food hygiene and safety training. About 81.25% of participants did not wear safety clothes during juice processing. The laboratory investigation of avocado fruit juice microbial load revealed a mean count of 5.43 log10 cfu/mL: aerobic mesophilic bacteria, 4.42 log10 cfu/mL: Staphylococcus, 4.35 log10 cfu/mL: total coliform, 4.40 log10 cfu/mL: Enterobacteriaceae, and 3.40log cfu/mL: yeast–mold. There was no statistical difference among the microbial load of fruit juice samples. The highest mean microbial load was found in the aerobic mesophilic count of 5.43log cfu/mL, while the lowest mean microbial load was found in the yeast–mold count of 3.40 log cfu/mL. The findings indicated that all avocado fruit juice mean microbial counts were higher than the recommended Gulf region standard. Juice handlers should receive regular training and education on food hygiene and safety to reduce the microbial loads of fruit juice.
Response in Patients With Persistent Pelvic Pain to Motor Imagery Through Auditory or Visual Input—A Pilot Randomized Trial
Authors: Perez-Dominguez Borja , Arce-Elorza Alba , Rubio-Garcia Isabel , Diaz-Mohedo Esther
Published: February 2025

Purpose: This study evaluates the response to a motor imagery intervention using visual or auditory inputs in patients with persistent pelvic pain. A secondary objective is to assess how patients’ mental visualization capacity influences intervention outcomes.

Methods: Forty patients diagnosed with persistent pelvic pain were enrolled in a randomized trial with six motor imagery sessions over 2 weeks. Patients were assigned to interventions delivered through images or audio recordings. Pain intensity, attention to pain, and the ability to mentally visualize and perceive movements were assessed.

Results: Participants receiving auditory stimulus–based interventions showed a nonsignificant reduction in pain intensity (from 7.1 points [SD: 1.9] to 6.1 points [SD: 2.4]; p = 0.091), while those in the visual input group experienced no change. Attention to pain improved in the visual group (from 30.2 points [SD: 6.2] to 27.6 points [SD: 6.8]; p = 0.194), whereas it remained stable in the auditory group. Importantly, the participants’ ability to mentally visualize and perceive movements did not significantly impact the outcomes.

Conclusions: Auditory motor imagery appears to be a promising, less intrusive approach for managing persistent pelvic pain, with home‐based interventions showing potential where access to conventional care is limited. This study highlights the importance of personalized motor imagery approaches, demonstrating superior efficacy for auditory interventions compared to visual ones. Limitations include a brief intervention period and recruitment challenges, yet motor imagery remains a viable therapeutic option.

Trial Registration: ClinicalTrials.gov identifier: NCT06343649
Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve is a Therapeutic Strategy for Pancreatic Cancer
Authors: DeLiberty Jonathan M. , Roach Mallory K. , Stalnecker Clint A. , Robb Ryan , Schechter Elyse G. , Pieper Noah L. , Taylor Khalilah E. , Pita Lily M. , Yang Runying , Bang Scott , Drizyte-Miller Kristina , Ackermann Sarah E. , Nicewarner Peña Sheila R. , Baldelli Elisa , Min Sophia M. , Drewry David H. , Petricoin Emanuel F. , Morris John P. , Der Channing J. , Cox Adrienne D. , Bryant Kirsten L.
Published: February 2025

Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux and dependency, and concurrent treatment with the nonspecific autophagy inhibitor chloroquine (CQ) and ERK-MAPK pathway inhibitors can synergistically block PDAC growth. However, CQ is limited in terms of specificity and potency. To find alternative anti-autophagy strategies, here we performed a CRISPR-Cas9 loss-of-function screen in PDAC cell lines that identified the lipid kinase PIKfyve as a growth-promoting gene. PIKfyve inhibition by the small molecule apilimod resulted in durable growth suppression, with much greater potency than CQ treatment. PIKfyve inhibition caused lysosomal dysfunction, reduced autophagic flux, and led to the accumulation of autophagy-related proteins. Furthermore, PIKfyve inhibition blocked the compensatory increases in autophagic flux associated both with MEK inhibition and with direct RAS inhibition. Accordingly, combined inhibition of PIKfyve and the RAS-MAPK pathway showed robust growth suppression across a panel of KRAS-mutant PDAC models. Growth suppression was due, in part, to potentiated cell cycle arrest and induction of apoptosis following loss of IAP proteins. These findings indicate that concurrent inhibition of RAS and PIKfyve is a synergistic, cytotoxic combination that may represent a therapeutic strategy for PDAC.
The Brain-Penetrant Pan ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases
Authors: Ippolitov Danyyl , Lin Yi-Han , Spence Jeremy , Glogowska Aleksandra , Thanasupawat Thatchawan , Beiko Jason , Del Bigio Marc R. , Xu Xin , Wang Amy Q. , Williams Darian , Calvo Raul , Kapoor Abhijeet , Marugan Juan J. , Henderson Mark J. , Klonisch Thomas , Hombach-Klonisch Sabine
Published: February 2025

Brain metastasis occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with trastuzumab and HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in vivo models for HER2+ BCBM has curtailed the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis. Here, we generated and characterized a luminal B HER2+ BCBM cell model (BCBM94) isolated from a patient HER2+ brain metastasis. Repeated hematogenic xenografting of BCBM94 consistently generated BCBM in mice. The clinical receptor tyrosine kinase inhibitor (RTKi) lapatinib blocked phosphorylation of all ErbB receptors (ErbB1-4) and induced the intrinsic apoptosis pathway in BCBM94. Neuregulin-1 (NRG1), an ErbB3/ErbB4 ligand that is abundantly expressed in the brain, abrogated lapatinib-induced apoptosis in HER2+ BCBM94 and BT474 models. ErbB3 signaling pathways that involved PI3K-AKT and the phosphorylation of BAD at serine 136 to prevent apoptosis were essential for NRG1-induced survival. High throughput RTKi screening identified the brain-penetrant pan-ErbB inhibitor poziotinib as a highly potent compound that reduced cell viability in HER2+ BCBM in the presence of NRG1. Two weeks of poziotinib treatment successfully ablated BCBM94 and BT474 HER2+ brain tumors in vivo. In conclusion, this study established a patient-derived HER2+ BCBM model and identified poziotinib as highly efficacious RTKi with excellent brain penetrability that eliminated HER2+ BCBM.