bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposomal bupivacaine in transversus abdominis plane blocks for lower abdominal surgery
Authors: Osuchukwu Obiyo , Gagnon James , Richard Janelle , Craig Wendy , Quaye Aurora
Published: January 2024

Background

Transversus abdominis plane blocks are an established method of postoperative analgesia for abdominopelvic surgeries. Liposomal bupivacaine is an extended‐release formulation of bupivacaine providing up to 72 h of analgesia. This study aims to determine if transversus abdominis plane blocks performed with liposomal bupivacaine are associated with reduced opioid consumption and level of pain intensity compared to conventional bupivacaine in patients undergoing lower abdominal surgery.

Methods

This retrospective cohort study was conducted at a single institution between December 2020 and December 2021. After institutional review board approval, we identified patients who underwent lower abdominopelvic surgery with transversus abdominis plane blocks done with liposomal or conventional bupivacaine and collected demographic, clinical, and procedural information for analysis. We compared total opioid consumption over 72‐h postoperatively in milligram morphine equivalents (MME), frequency of opioid utilization, and average level of pain intensity between groups. These outcomes were also evaluated after adjusting for covariates. Data were presented as mean ± SD, median [IQR] or frequency (%), as appropriate; p < 0.05 was accepted as significant.

Results

A total of 178 patients met inclusion criteria, with 79 patients receiving an admixture of liposomal bupivacaine and conventional bupivacaine and 99 patients receiving conventional bupivacaine. The liposomal bupivacaine group had a median opioid consumption 72‐h postoperatively of 47.5 [18–91.8] MME compared to 88 [43.8–160] MME in the conventional bupivacaine group, p = 0.045. Differences in opioid consumption between the groups did not reach statistical significance after adjustment for demographic and clinical characteristics, p = 0.11. There was no significant difference in frequency of opioid use or average pain intensity.

Conclusion

Transversus abdominis plane blocks using an admixture of liposomal bupivacaine conventional bupivacaine are not associated with decreased opioid consumption or reduced pain up to 72 h following elective abdominopelvic surgery.
Effectiveness of motor imagery in complex regional pain syndrome: A systematic review with meta‐analysis
Authors: Ríos‐León Marta , Cuñado‐González Álvaro , Domínguez‐Fernández Silvia , Martín‐Casas Patricia
Published: January 2024

Objective

The purpose of this study was to determine the effects of motor imagery (MI) on pain intensity and disability in individuals with complex regional pain syndrome (CRPS).

Methods

A systematic search was conducted in various electronic databases to identify all relevant studies: PubMed, CINAHL, WOS, PEDro, CENTRAL, and Scopus. Randomized controlled trials assessing the effects of MI in individuals with CRPS were included. The risk of bias was assessed with the Cochrane Risk of Bias tool, the methodological quality was evaluated using PEDro scale, and the level of evidence was reported according to the GRADE. Between‐groups standardized mean differences (SMD) were calculated.

Results

Six studies were included. The meta‐analysis found moderate‐quality evidence that MI improves pain intensity and related disability as immediate (pain: SMD −1.07, 95% CI: −1.53 to −0.60; disability: SMD 1.05, 95% CI: 0.59 to 1.51), short‐term (pain: SMD −1.28, 95% CI: −2.14 to −0.42; disability: SMD 1.37; 95% CI: 0.16 to 2.58), and long‐term effects (pain: SMD −1.18; 95% CI: −1.89 to −0.46; disability: SMD 1.18; 95% CI: 0.46 to 1.89), as compared with a comparison group. The risk of bias of the trials was relatively low, but the imprecision of the results downgraded the level of evidence.

Conclusions

Moderate‐quality evidence suggests a positive effect of MI for improving pain intensity and disability immediately after and at short‐term in individuals with CRPS.
Comparison of different methods of screening to identify intimate partner violence: A randomized controlled trial
Authors: Sharps Phyllis , Bullock Linda , Perrin Nancy , Campbell Jacquelyn , Hill Kimberly , Kanu Iye , Norling Meg , Russell Nancy G.
Published: January 2024

Objective

Screening for intimate partner violence in the home is often challenging due to the lack of privacy. The aim of this study was to compare two different screening methods (paper‐pencil vs. tablet) for identifying intimate partner violence during perinatal home visits.

Design

Randomized control trial.

Sample

Pregnant women (N = 416) in perinatal home visiting programs were randomized to either paper‐pencil or computer assisted, intimate partner violence screening.

Measurements

The Abuse Assessment Screen was used to screen for physical and sexual IPV and Women's Experiences with Battering for emotional intimate partner violence.

Results

No significant differences in prevalence were found between the screening methods. Intimate partner violence prevalence rates for the year before and/or during pregnancy using paper‐pencil was 21.8% versus 24.5% using tablets (p = .507). There were significant differences in prevalence among the three race/ethnic groups (Caucasian, 36.9%; African American, 26.7%; Hispanics, 10.6%; p < .001) and significant differences in rates across three geographical areas: urban 16.0%; rural 27.6%, suburban women 32.3% (p < .001).

Conclusions

This study provides evidence that both methods are useful for identifying intimate partner violence during perinatal home visits.
Role of innate host defense proteins in oral cancerogenesis
Authors: Winter Jochen , Jepsen Søren
Published: January 2024

It is nowadays well accepted that chronic inflammation plays a pivotal role in tumor initiation and progression. Under this aspect, the oral cavity is predestined to examine this connection because periodontitis is a highly prevalent chronic inflammatory disease and oral squamous cell carcinomas are the most common oral malignant lesions. In this review, we describe how particular molecules of the human innate host defense system may participate as molecular links between these two important chronic noncommunicable diseases (NCDs). Specific focus is directed toward antimicrobial polypeptides, such as the cathelicidin LL‐37 and human defensins, as well as S100 proteins and alarmins. We report in which way these peptides and proteins are able to initiate and support oral tumorigenesis, showing direct mechanisms by binding to growth‐stimulating cell surface receptors and/or indirect effects, for example, inducing tumor‐promoting genes. Finally, bacterial challenges with impact on oral cancerogenesis are briefly addressed.
The politics of problems versus solutions: Policymaking and grandstanding in congressional hearings
Authors: Lewallen Jonathan , Park Ju Yeon , Theriault Sean M.
Published: January 2024

Several theories of policy change posit that the politics of defining and prioritizing problems differs from the politics of devising and selecting solutions. The former involves simplifying through heuristics like indicators and ideology while the latter incorporates policy analysis and expertise to a greater degree. By employing two large datasets of U.S. congressional hearings to analyze policymakers' behavior of sending political messages, which we call “grandstanding,” we offer two findings. First, consistent with our hypotheses, grandstanding is more prevalent when committees are focused on new and emerging problems than when committees examine proposed alternatives or the implementation of existing policies. Second, the cognitive dynamics of problem solving and the incentives to grandstand vary depending on policy issues considered in hearings. Our analysis helps put dissatisfaction with contemporary U.S. policymaking in context: a rise in “messaging politics” derives at least in part from an increased focus on contesting the problem space in agenda‐setting venues.
Older people and care networks in rural areas: An exploratory study in Italy
Authors: Arlotti Marco
Published: January 2024

A care crisis concept has been introduced in the literature to describe the growing decoupling process between the expanding care needs of older people and the difficulties of informal and family networks in coping. These changes happened in rural areas quicker and with greater intensity than in urban areas.Against this background, the article investigates older people living in rural areas in Italy and focuses on care networks. The analysis draws on an exploratory study conducted in three rural areas, based on 48 interviews with older people living alone at home and with different degrees of functional limitations and care needs.The research findings highlight the emergence of a complex scenario characterised by different configurations of care networks and coping strategies of adaptation and reorganisation. At the same, the research suggests further research lines to capture the multifaceted dimensions and multiple inequalities related to the care crisis in rural areas.
A Hybrid Method Combining Data-Driven and Model-Based Algorithms for External Force-Sensing and Haptics Control of Cable-Pulley-Driven Surgical Robotic Manipulator
Authors: Wang Zhengyu , Yu Xiang , Hai Mingxin , Qian Sen , Wang Daoming , Li Ziqian
Published: January 2024

The implementation of the high-precision tracking control and external force-sensing ability of a manipulator is important for achieving refined surgical robot operation. In this paper, a hybrid method based on data-driven and model-based algorithms is proposed for the manipulator of a cable-pulley-driven surgical robot. This method integrates an artificial neural network and a dynamic model rotation angle estimation, and a full closed-loop control architecture is further constructed. The algorithm compensates for the hysteresis of the joint angle and effectively improves the tracking control precision. Based on the architecture, the external force estimator (EFE) using a joint torque disturbance observer and the force interaction teleoperation control strategy using a direct force feedback framework (DFF) are implemented. In the force loading experiment, it was shown that the EFE performs well for static and dynamic force estimation, and the teleoperated haptic control experiment showed that the DFF-EFE-based system has a high position-tracking accuracy with real-time external force-sensing ability.
Impact of the Bars Behavior on the Design of Soft Tensegrities
Authors: Sand Jérémy , Geiskopf François , Abdelaziz Salih , Poignet Philippe , Renaud Pierre
Published: January 2024

Soft tensegrity is a recent concept, which can be described as a prestressed assembly of soft cables in tension and bars in compression. In this paper, we investigate the impact of the bar behavior on the mechanical properties of a tensegrity. This is achieved through the change of bar material, from soft (e.g., silicone) to stiff (e.g., steel) materials. First, we show that it is possible to make a self-supporting tensegrity where both cables and bars are made of soft material. Second, we highlight that the bar material impacts the isotropy of the stiffness matrix of the tensegrity and the range of achievable stiffness. Lastly, we demonstrate that the bar material has a significant impact on the precision of stiffness variation, when active elements are integrated into the tensegrity. From these effects, we extract design guidelines for the choice of bar material in a soft tensegrity.
Sensitivity Analysis of Performance Tests for Six-Degree-of-Freedom Serial Industrial Robots
Authors: Wang Ling , Wu Xiaoliang , Gao Yanfeng , Chen Xiai , Wang Binrui
Published: January 2024

The international standard ISO 9283:1998 is popular for performance tests of industrial robots at present. It is desirable that the tests described in this standard should be sensitive to error sources of robot end positioning/orientation. In this paper, first, the kinematic and the joint stiffness model parameters are identified experimentally for two models of six-DOF (degree-of-freedom) serial industrial robots (i.e., the ABB IRB 1410 and UR5 robots). Then, the standard deviations of the derived model parameters are obtained as error inputs for the sensitivity analysis of the performance tests including the positioning/orientation accuracy/repeatability tests. By simulating the error sensitivity of the positioning/orientation accuracy/repeatability test methods for industrial robots, it is analyzed whether the tests described in the ISO 9283:1998 Standard are sensitive to the focused error sources, showing the limitations of the evaluation index of the ISO 9283:1998 Standard. The results show that for six-DOF serial industrial robots, the positioning accuracy test is the key to determining their motion performance. The orientation accuracy and repeatability tests are not necessary if the positioning accuracy and repeatability tests can be done for six-DOF serial industrial robots. Finally, the improvement suggestion of the performance test method is proposed. The research of this paper is beneficial for improving the performance evaluation methods of industrial robots. It can also help robot manufacturing enterprises analyze and improve the positioning/orientation accuracy/repeatability of their products.
A pressure solution flow law for the seismogenic zone: Application to Cascadia
Authors: Fisher Donald M. , Hirth Greg
Published: January 2024

We develop a linear viscous constitutive relationship for pressure solution constrained by models of deformed metasedimentary rocks and observations of exposed rocks from ancient subduction zones. We include pressure and temperature dependence on the solubility of silica in fluid by parameterizing a practical van’t Hoff relationship. This general flow law is well suited for making predictions about interseismic behavior of subduction zones. We apply the flow law to Cascadia, where thermal structure, geometry, relative plate velocity, and Global Positioning System velocity field are well constrained. Results are consistent with the temperature conditions at which resolvable ductile strain is recorded in subducted mudstones (at depths near the updip limit of the seismogenic zone) and with relative plate motion accommodated completely by viscous deformation (at depths near the downdip limit of the seismogenic zone). The flow law also predicts the observed forearc tapering of slip rate deficit with depth.
Regulatory evolution tuning pigmentation intensity quantitatively in
Drosophila
Authors: Bachem Katharina , Li Xinyi , Ceolin Stefano , Mühling Bettina , Hörl David , Harz Hartmann , Leonhardt Heinrich , Arnoult Laurent , Weber Sabrina , Matarlo Blair , Prud’homme Benjamin , Gompel Nicolas
Published: January 2024

Quantitative variation in attributes such as color, texture, or stiffness dominates morphological diversification. It results from combinations of alleles at many Mendelian loci. Here, we identify an additional source of quantitative variation among species, continuous evolution in a gene regulatory region. Specifically, we examined the modulation of wing pigmentation in a group of fly species and showed that inter-species variation correlated with the quantitative expression of the pigmentation gene
yellow
. This variation results from an enhancer of
yellow
determining darkness through species-specific activity. We mapped the divergent activities between two sister species and found the changes to be broadly distributed along the enhancer. Our results demonstrate that enhancers can act as dials fueling quantitative morphological diversification by modulating trait properties.
A self-organizing robotic aggregate using solid and liquid-like collective states
Authors: Saintyves Baudouin , Spenko Matthew , Jaeger Heinrich M.
Published: January 2024

Designing robotic systems that can change their physical form factor as well as their compliance to adapt to environmental constraints remains a major conceptual and technical challenge. To address this, we introduce the Granulobot, a modular system that blurs the distinction between soft, modular, and swarm robotics. The system consists of gear-like units that each contain a single actuator such that units can self-assemble into larger, granular aggregates using magnetic coupling. These aggregates can reconfigure dynamically and also split into subsystems that might later recombine. Aggregates can self-organize into collective states with solid- and liquid-like properties, thus displaying widely differing compliance. These states can be perturbed locally via actuators or externally via mechanical feedback from the environment to produce adaptive shape-shifting in a decentralized manner. This, in turn, can generate locomotion strategies adapted to different conditions. Aggregates can move over obstacles without using external sensors or coordinates to maintain a steady gait over different surfaces without electronic communication among units. The modular design highlights a physical, morphological form of control that advances the development of resilient robotic systems with the ability to morph and adapt to different functions and conditions.
Single-cell atlas of human infrapatellar fat pad and synovium implicates APOE signaling in osteoarthritis pathology
Authors: Tang Su’an , Yao Lutian , Ruan Jianzhao , Kang Jingliang , Cao Yumei , Nie Xiaoyu , Lan Weiren , Zhu Zhaohua , Han Weiyu , Liu Yongguang , Tian Jing , Seale Patrick , Qin Ling , Ding Changhai
Published: January 2024

The infrapatellar fat pad (IPFP) and synovium play essential roles in maintaining knee joint homeostasis and in the progression of osteoarthritis (OA). The cellular and transcriptional mechanisms regulating the function of these specialized tissues under healthy and diseased conditions are largely unknown. Here, single-cell and single-nuclei RNA sequencing of human IPFP and synovial tissues were performed to elucidate the cellular composition and transcriptional profile. Computational trajectory analysis revealed that dipeptidyl peptidase 4
+
mesenchymal cells function as a common progenitor for IPFP adipocytes and synovial lining layer fibroblasts, suggesting that IPFP and synovium represent an integrated tissue unit. OA induced a profibrotic and inflammatory phenotype in mesenchymal lineage cells with biglycan
+
intermediate fibroblasts as a major contributor to OA fibrosis. Apolipoprotein E (APOE) signaling from intermediate fibroblasts and macrophages was identified as a critical regulatory factor. Ex vivo incubation of human cartilage with soluble APOE accelerated proteoglycan degeneration. Inhibition of APOE signaling by intra-articular injection of an anti-APOE neutralizing antibody attenuated the progression of collagenase-induced OA in mice, demonstrating a detrimental effect of APOE on cartilage. Our studies provide a framework for designing further therapeutic strategies for OA by describing the cellular and transcriptional landscape of human IPFP and synovium in healthy versus OA joints.
Paediatric shadowing: a student-led initiative to increase medical student interest in paediatric careers
Authors: Zaloum Safiya A , Kherati Rida , Khun Sokhun Solyndar , Ng Amy Yi-Lin , Przypasniak Zofia , Ravimani Sowjenya , Morrissey Benita , Minson Susie
Published: January 2024

Introduction

Clinical exposure to paediatrics increases student interest in the specialty. However, the paediatric placement is relatively short and usually falls towards the end of medical school in the UK. A student-led shadowing scheme was developed to provide opportunities for medical students, including those at an early stage, to experience clinical paediatrics.

Methods

Paediatric society members could apply for a shadowing day in the scheme run in 2022 and 2023. Feedback was collected following the day. Free text answers on learning points and the impact of shadowing on views of paediatrics were analysed using a framework approach. Knowledge of the role of a paediatrician and consideration of a career in paediatrics were rated on a 5-point Likert scale before and after the shadowing day.

Results

66 and 37 students completed shadowing days in cycles 1 and 2, respectively. Students’ knowledge of the role of the paediatrician and consideration of a career in paediatrics increased significantly after the shadowing scheme. The key themes that participating year 1–2 students gained from the scheme were: increased interest in paediatrics, increased knowledge about the specialty, challenges and decision-making in paediatrics, variety within paediatrics, communication skills, working with families, improving practical skills and some overwhelming first clinical experiences.

Discussion

A student-run shadowing scheme is a novel and sustainable way to provide early exposure to paediatrics in medical school. This will help to develop interest in paediatrics from the start of medical school, as clinical exposure is a key factor in choosing paediatrics once qualified.
Recognition, prevention and management of ‘digital harm’
Authors: Joustra Arthur , Quinn Lauren , Walker Vicki
Published: January 2024

The digital world continues to evolve and is apparent in all aspects of daily life. For children and young people, their online life is as real to them as their in-person life. Health professionals urgently need to update their knowledge and awareness of the positive and negative impacts of the myriad of online content and how this is viewed and used by children and young people. Digital harm can contribute to multiple clinical presentations and paediatricians must ask about online life in consultations and be able to provide holistic digital safety advice, while recognising serious digital harm requiring safeguarding input.

This article will introduce the main areas of harm and how to include assessment in routine clinical practice. It will equip paediatricians to offer advice and safeguard children and young people and offer resources and links to further learning.
Perceptions of and responses of young adults who use e-cigarettes to flavour bans in China: a qualitative study
Authors: Weng Xue , Song Chu Yu , Liu Kefeng , Wu Yongda Socrates , Lee Jung Jae , Guo Ningyuan , Wang Man Ping
Published: January 2024

Background

China has banned all flavoured e-cigarettes to reduce e-cigarette use among young people, but little is known about the views and reactions of people who use e-cigarettes. This study explored the perceptions of, and responses by, young adults who use e-cigarettes to the flavour ban.

Methods

Semistructured interviews were conducted with 25 Chinese young adults aged 18–25 years who had used e-cigarettes daily in the past 3 months. Thematic analysis was used to analyse the interview data.

Findings

Four themes were identified from the data: (1) understanding of the public health benefits, (2) resistance to and misperceptions of the flavour ban, (3) circumvention of the flavour ban and (4) acceptance of the flavour ban. Some participants expressed support for the ban due to perceived public health benefits, while others who resisted the ban emphasised their right to choose preferred flavours and questioned the rationale behind the policy. Participants responded to the flavour ban by utilising a variety of adaptive strategies, including purchasing flavoured e-cigarettes through illegal channels or exploring alternative ways to obtain flavours. Those who complied with the ban responded with different strategies, including switching back to combustible cigarettes, using tobacco-flavoured e-cigarettes, or quitting vaping.

Conclusions

The findings suggest the need for comprehensive regulatory measures, including stringent enforcement measures, transparent health communication and vigilant monitoring of e-cigarette manufacturers’ tactics, to reduce e-cigarette use among young adults.
Source Network Load Storage Access to Power Wireless Private Network Technology Based on 5G Ultra Dense Networking
Authors: Liu Zehui , Ma Dongjuan , Guo Min , Jing Weizhe , Gao Wei , Kong Weikang
Published: January 2024

We make the source network load storage access power wireless private network, this paper proposes a source network load storage access power wireless private network technology based on 5G ultra dense network. The multiple rotation scheduling and self-organizing learning methods are used to establish the deployment model of the source network load storage access node of the power wireless private network under the 5G communication mode. According to the routing control algorithm design of the 5G ultra dense networking node, combined with the integration analysis of the access load parameters, the source network load storage access model of the 5G ultra dense networking under the dynamic load distributed control mode is established. Through the method of optimal control of reactive power and voltage of distribution network, the transmission link equilibrium structure model of 5G source network load storage access to power wireless private network is constructed. Combined with the coverage analysis of link topology structure and the benefit maximization constraint analysis of production and consumption users, the active and reactive capacity analysis of transaction between production and consumption user groups and multiple production and consumption users is adopted. Combined with the energy storage characteristics analysis and power flow parameter calculation of the source network load storage access power, the 5G ultra dense networking and private network access to the source network load storage access power are realized. The test shows that this method has better power balance dispatching ability and larger output power gain when it is applied to the design of source network load storage access power wireless private network.
Design and Implementation of Data Management and Visualisation Module in Financial Digital Management
Authors: Ren Junying
Published: January 2024

Enterprise financial data is the key indicator of enterprise development, which provides the important basis for management to analyse and make decisions. Therefore, the provision of reliable and effective information services to enterprises through visualisation technology has become an urgent problem to be solved in the construction of enterprise informatisation. At present, the common data statistics and visualisation tools in the market are difficult to meet the needs of specialised financial enterprises for data analysis. Additionally, the current financial management system has several issues, including an abundance of data and lack of observation suitability. Aiming at the deficiency of data management function in the system, this paper studies the improvement design of data management and visualisation module in financial digital management. First, [Formula: see text]-means clustering algorithm and C4.5 decision tree algorithm are selected to improve the financial data management system. Then, through the existing hierarchical data visualisation scheme, the node link method, space filling method and Sankey chart are proposed to display the changes of financial data. Finally, the data management and visualisation module and the corresponding algorithm flow are designed. The experiment indicates a contour coefficient of 0.53 for the performance evaluation model based on the [Formula: see text]-means algorithm, indicating a satisfactory clustering result. The employee violation prediction model, based on the C4.5 decision tree algorithm, exhibits a high prediction accuracy of 92.35% for the training dataset, demonstrating its effectiveness in predicting employee violations. The data rendering accuracy of the visualised tool is 98.46%, significantly surpassing that of traditional visualisation tools. At the same time, its visual effect and operation are better than traditional tools. Compared with the traditional data visualisation system, this research method improves the efficiency of enterprise financial data management, converts complicated financial data into graphics that are easier for people to understand, realises visualisation, and effectively reduces the management cost of financial operations.
Mouse Dynamics Behavioral Biometrics: A Survey
Authors: Khan Simon , Devlen Charles , Manno Michael , Hou Daqing
Published: January 2024

Utilization of the Internet in our everyday lives has made us vulnerable in terms of privacy and security of our data and systems. Therefore, there is a pressing need to protect our data and systems by improving authentication mechanisms, which are expected to be low cost, unobtrusive, and ideally ubiquitous in nature. Behavioral biometric modalities such as mouse dynamics (mouse behaviors on a graphical user interface (GUI)) and widget interactions (another modality closely related to mouse dynamics that also considers the target (widget) of a GUI interaction, such as links, buttons, and combo-boxes) can bolster the security of existing authentication systems because of their ability to distinguish individuals based on their unique features. As a result, it can be difficult for an imposter to impersonate these behavioral biometrics, making them suitable for authentication. In this article, we survey the literature on mouse dynamics and widget interactions dated from 1897 to 2023. We begin our survey with an account of the psychological perspectives on behavioral biometrics. We then analyze the literature along the following dimensions: tasks and experimental settings for data collection, taxonomy of raw attributes, feature extractions and mathematical definitions, publicly available datasets, algorithms (statistical, machine learning, and deep learning), data fusion, performance, and limitations. We end the paper with presenting challenges and promising research opportunities.
Exploring Semantic Redundancy using Backdoor Triggers: A Complementary Insight into the Challenges Facing DNN-based Software Vulnerability Detection
Authors: Shao Changjie , Li Gaolei , Wu Jun , Zheng Xi
Published: January 2024

To detect software vulnerabilities with better performance, deep neural networks (DNNs) have received extensive attention recently. However, these vulnerability detection DNN models trained with code representations are vulnerable to specific perturbations on code representations. This motivates us to rethink the bane of software vulnerability detection and find function-agnostic features during code representation which we name as semantic redundant features. This paper first identifies a tight correlation between function-agnostic triggers and semantic redundant feature space (where the redundant features reside) in these DNN models. For correlation identification, we propose a novel Backdoor-based Semantic Redundancy Exploration (BSemRE) framework. In BSemRE, the sensitivity of the trained models to function-agnostic triggers is observed to verify the existence of semantic redundancy in various code representations. Specifically, acting as the typical manifestations of semantic redundancy, naming conventions, ternary operators and identically-true conditions are exploited to generate function-agnostic triggers. Extensive comparative experiments on 1,613,823 samples of eight representative vulnerability datasets and state-of-the-art code representation techniques and vulnerability detection models demonstrate that the existence of semantic redundancy determines the upper trustworthiness limit of DNN-based software vulnerability detection. To the best of our knowledge, this is the first work exploring the bane of software vulnerability detection using backdoor triggers.
Trinity: High-Performance and Reliable Mobile Emulation through Graphics Projection
Authors: Lin Hao , Li Zhenhua , Gao Di , Liu Yunhao , Qian Feng , Xu Tianyin , Xiao Bo , Qin Xiaokang
Published: January 2024

Mobile emulation, which creates full-fledged software mobile devices on a physical PC/server, is pivotal to the mobile ecosystem. Unfortunately, existing mobile emulators perform poorly on graphics-intensive apps in terms of efficiency and compatibility. To address this, we introduce
graphics projection
, a novel graphics virtualization mechanism that adds a small-size
projection space
inside the guest memory, which processes graphics operations involving control contexts and resource handles without host interactions. While enhancing performance, the decoupled and asynchronous guest/host control flows introduced by graphics projection can significantly complicate emulators’ reliability issue diagnosis when faced with a variety of uncommon or non-standard app behaviors in the wild, hindering practical deployment in production. To overcome this drawback, we develop an automatic reliability issue analysis pipeline that distills the critical code paths across the guest and host control flows by runtime quarantine and state introspection. The resulting new Android emulator, dubbed Trinity, exhibits an average of 97% native hardware performance and 99.3% reliable app support, in some cases outperforming other emulators by more than an order of magnitude.
Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury
Authors: Jaeschke Hartmut , Ramachandran Anup
Published: January 2024

Acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity in western countries, and, because of translational relevance of animal models, APAP is mechanistically the most studied drug. This review covers intracellular signaling events starting with drug metabolism and the central role of mitochondrial dysfunction involving oxidant stress and peroxynitrite. Mitochondria-derived endonucleases trigger nuclear DNA fragmentation, the point of no return for cell death. In addition, adaptive mechanisms that limit cell death are discussed including autophagy, mitochondrial morphology changes, and biogenesis. Extensive evidence supports oncotic necrosis as the mode of cell death; however, a partial overlap with signaling events of apoptosis, ferroptosis, and pyroptosis is the basis for controversial discussions. Furthermore, an update on sterile inflammation in injury and repair with activation of Kupffer cells, monocyte-derived macrophages, and neutrophils is provided. Understanding these mechanisms of cell death led to discovery of N-acetylcysteine and recently fomepizole as effective antidotes against APAP toxicity.
Coherent olfactory bulb gamma oscillations arise from coupling independent columnar oscillators
Authors: Peace Shane T. , Johnson Benjamin C. , Werth Jesse C. , Li Guoshi , Kaiser Martin E. , Fukunaga Izumi , Schaefer Andreas T. , Molnar Alyosha C. , Cleland Thomas A.
Published: January 2024

Odor stimulation evokes rhythmic gamma oscillations in the field potential of the olfactory bulb, but the dynamical mechanisms governing these oscillations have remained unclear. Establishing these mechanisms is important as they determine the biophysical capacities of the bulbar circuit to, for example, maintain zero-phase coherence across a spatially extended network, or coordinate the timing of action potentials in principal neurons. These properties in turn constrain and suggest hypotheses of sensory coding.
“We Were Held in Bondage”: A Case Study on Grandparents Raising Grandchildren in Skipped Generations in Rural Northern Thailand
Authors: Kodyee Salisa , Moonpanane Katemanee , Thepsaw Jintana , Wuttipan Nathamon
Published: January 2024

Although grandparents play a significant role in caring for their grandchildren in Asian culture, few studies have examined how grandparents from skipped families care for their children in rural areas. This study aims to explore grandparents’ perceptions and experiences in providing care for their grandchildren in rural Thailand, where support is limited. Utilizing a qualitative approach, in‐depth interviews and focus group discussions were conducted with 20 grandparents caring for children under 5 years old. The coding of interview transcripts was followed by thematic analysis. In this study, the participants shared their experiences about raising and caring for their grandchildren in rural areas. “We were held in bondage” is the overarching theme. Interviews revealed two main themes: (1) feeling of burden, divided into the following three subthemes: lack of parenting skills, worries regarding grandchildren’s health and well‐being, and emotional stress and financial/physical strain; (2) maintaining family bonds, which were further divided into the following subthemes: supporting adult children, being parents again, and becoming more loving and bonded. According to the findings, healthcare providers may be able to anticipate the needs of grandparents in rural areas and provide support, culturally relevant interventions, and training programs for grandparents to care for their grandchildren. Further research is essential to explore the dynamics of family bonding and responsibilities in Thai families and to develop interventions supporting these families.
Photoprotective Effects of Epigallocatechin Gallate on Ultraviolet-Induced Zebrafish and Human Skin Fibroblasts Cells
Authors: Zhang Jie , Xu Yahui , Ruan Xiyu , Zhang Ting , Zi Minghui , Zhang Qiao
Published: January 2024

Background. The long-term exposure to ultraviolet radiation (UVR) raises oxidative stress and chronic inflammation levels, which in turn has a series of deleterious effects on skin health, such as sunburn, photoaging, and skin cancer. Hence, our study was determined to investigate the effects and mechanisms of epigallocatechin gallate (EGCG) in zebrafish and human skin fibroblasts (HSF) cells to alleviate ultraviolet-induced photoaging. Methods. The 4 days postfertilization (dpf) zebrafish larvae and HSF cells were treated with 10 J/cm2 UVA + 30 mJ/cm2 UVB, or 25, or 50 μM EGCG for 72 hr. The indicators involving in oxidative stress, inflammatory, and photoaging were measured by the kits, ELISA Kits and western blot methods. Results. EGCGs protect against UVR-induced skin damage in zebrafish and HSF cells. EGCG markedly decreased the reactive oxygen species (ROS), malondialdehyde, 8-OHdG levels, increased superoxide dismutase (SOD) activity, and significantly inhibited inflammatory factors levels including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) in zebrafish, and HSF cells irradiated with UVR. We found that EGCG could reduce UVR-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-κB (NF-κB), thereby reducing the protein-1 (AP-1), TNF-α, IL-1α, IL-6, and matrix metalloproteinase-1 (MMP-1) expressions, which are critical mediators of skin aging cascade causing the photoaging. Conclusion. These results validate that EGCG for protection of photoaging in zebrafish and HSF cells induced by UVR, which is closely related to the regulation of p38 MAPK/NF-κB, AP-1 signaling pathway which relieve oxidative stress, inflammation, and collagen degradation.
TFE3-Splicing Factor Fusions Represent Functional Drivers and Druggable Targets in Translocation Renal Cell Carcinoma
Authors: Damayanti Nur P. , Cordova Ricardo A. , Rupert Christopher , Delle Fontane Ilaria , Shen Li , Orsi Sabrina , Klunk Angela J. , Linehan W. Marston , Staschke Kirk A. , Hollenhorst Peter C. , Heppner David E. , Pili Roberto
Published: January 2024

TFE3 is a member of the basic helix–loop–helix leucine zipper MiT transcription factor family, and its chimeric proteins are associated with translocation renal cell carcinoma (tRCC). Despite the variety of gene fusions, most TFE3 fusion partner genes are related to spliceosome machinery. Dissecting the function of TFE3 fused to spliceosome machinery factors (TFE3-SF) could direct the development of effective therapies for this lethal disease, which is refractory to standard treatments for kidney cancer. Here, by using a combination of in silico structure prediction, transcriptome profiling, molecular characterization, and high-throughput high-content screening (HTHCS), we interrogated a number of oncogenic mechanisms of TFE3-SF fusions. TFE3-SF fusions drove the transformation of kidney cells and promoted distinct oncogenic phenotypes in a fusion partner-dependent manner, differentially altering the transcriptome and RNA splicing landscape and activating different oncogenic pathways. Inhibiting TFE3-SF dimerization reversed its oncogenic activity and represented a potential target for therapeutic intervention. Screening the FDA-approved drugs library LOPAC and a small-molecule library (Microsource) using HTHCS combined with FRET technology identified compounds that inhibit TFE3-SF dimerization. Hit compounds were validated in 2D and 3D patient-derived xenograft models expressing TFE3-SF. The antihistamine terfenadine decreased cell proliferation and reduced in vivo tumor growth of tRCC. Overall, these results unmask therapeutic strategies to target TFE3-SF dimerization for treating patients with tRCC.

Significance:

TFE3-splicing factor fusions possess both transcription and splicing factor functions that remodel the transcriptome and spliceosome and can be targeted with dimerization inhibitors to suppress the growth of translocation renal cell carcinoma.
Chromatin Remodelers Are Regulators of the Tumor Immune Microenvironment
Authors: Chaudhri Apoorvi , Lizee Gregory , Hwu Patrick , Rai Kunal
Published: January 2024

Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor-intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations with immune checkpoint inhibitors. Some success has been observed in early clinical studies that combined immunotherapy with agents targeting DNA methylation and histone modification; however, less is known about chromatin remodeler-targeted therapies. Here, we provide a discussion on the regulation of tumor immunogenicity by the chromatin remodeling SWI/SNF complex through multiple mechanisms associated with immunotherapy response that broadly include IFN signaling, DNA damage, mismatch repair, regulation of oncogenic programs, and polycomb-repressive complex antagonism. Context-dependent targeting of SWI/SNF subunits can elicit opportunities for synthetic lethality and reduce T-cell exhaustion. In summary, alongside the significance of SWI/SNF subunits in predicting immunotherapy outcomes, their ability to modulate the tumor immune landscape offers opportunities for therapeutic intervention.
Facts and Hopes in Immunotherapy Strategies Targeting Antigens Derived from KRAS Mutations
Authors: Linette Gerald P. , Bear Adham S. , Carreno Beatriz M.
Published: January 2024

In this commentary, we advance the notion that mutant KRAS (mKRAS) is an ideal tumor neoantigen that is amenable for targeting by the adaptive immune system. Recent progress highlights key advances on various fronts that validate mKRAS as a molecular target and support further pursuit as an immunological target. Because mKRAS is an intracellular membrane localized protein and not normally expressed on the cell surface, we surmise that proteasome degradation will generate short peptides that bind to HLA class I (HLA-I) molecules in the endoplasmic reticulum for transport through the Golgi for display on the cell surface. T-cell receptors (TCR)αβ and antibodies have been isolated that specifically recognize mKRAS encoded epitope(s) or haptenated-mKRAS peptides in the context of HLA-I on tumor cells. Case reports using adoptive T-cell therapy provide proof of principle that KRAS G12D can be successfully targeted by the immune system in patients with cancer. Among the challenges facing investigators is the requirement of precision medicine to identify and match patients to available mKRAS peptide/HLA therapeutics and to increase the population coverage by targeting additional mKRAS epitopes. Ultimately, we envision mKRAS-directed immunotherapy as an effective treatment option for selected patients that will complement and perhaps synergize with small-molecule mKRAS inhibitors and targeted mKRAS degraders.
Data from Systems Analysis of the NCI-60 Cancer Cell Lines by Alignment of Protein Pathway Activation Modules with “-OMIC” Data Fields and Therapeutic Response Signatures
Authors: Federici Giulia , Gao Xi , Slawek Janusz , Arodz Tomasz , Shitaye Amanuel , Wulfkuhle Julia D. , De Maria Ruggero , Liotta Lance A. , Petricoin Emanuel F.
Published: January 2024

Abstract
The NCI-60 cell line set is likely the most molecularly profiled set of human tumor cell lines in the world. However, a critical missing component of previous analyses has been the inability to place the massive amounts of “-omic” data in the context of functional protein signaling networks, which often contain many of the drug targets for new targeted therapeutics. We used reverse-phase protein array (RPPA) analysis to measure the activation/phosphorylation state of 135 proteins, with a total analysis of nearly 200 key protein isoforms involved in cell proliferation, survival, migration, adhesion, etc., in all 60 cell lines. We aggregated the signaling data into biochemical modules of interconnected kinase substrates for 6 key cancer signaling pathways: AKT, mTOR, EGF receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), integrin, and apoptosis signaling. The net activation state of these protein network modules was correlated to available individual protein, phosphoprotein, mutational, metabolomic, miRNA, transcriptional, and drug sensitivity data. Pathway activation mapping identified reproducible and distinct signaling cohorts that transcended organ-type distinctions. Direct correlations with the protein network modules involved largely protein phosphorylation data but we also identified direct correlations of signaling networks with metabolites, miRNA, and DNA data. The integration of protein activation measurements into biochemically interconnected modules provided a novel means to align the functional protein architecture with multiple “-omic” data sets and therapeutic response correlations. This approach may provide a deeper understanding of how cellular biochemistry defines therapeutic response. Such “-omic” portraits could inform rational anticancer agent screenings and drive personalized therapeutic approaches. Mol Cancer Res; 11(6); 676–85. ©2013 AACR.