bluuebunny/crossref_metadata_2025 huggingface dataset:
Review on the protection properties of thermal protective clothing against hot liquids and steam
Authors: Yu Xiaokun , Xue Fei , Zhu Dahui , Ke Yonghui
Published: December 2024

Professionals engaged in fire rescue and industrial production may face the danger of hot liquids and steam. They need to be equipped with specific thermal protective clothing (TPC) to ensure their safety. To evaluate how well TPC protects against hot liquids and steam, this paper reviewed the mechanism of hot liquids and steam, the factors affecting its protection, and measurement methods. Firstly, the characteristics of hot liquids and steam are analyzed from the perspective of heat transfer mode, and the importance of hot liquids and steam protection is emphasized. Secondly, the factors affecting protection performance of hot liquids and steam is reviewed base on relevant researches, focusing on the fundamental properties of fabrics, the air layer under clothing, the moisture factor, clothing factor and the environmental factor. Finally, the existing measurement methods for hot liquid and steam protection performance are summarized, and the deficiencies in the existing research has been discussed. At last, this paper looks forward to the development of the future research direction. This review provides reference ideas for protective measures against hot liquid and steam burns, and provides new ideas for the design and optimization of hot liquid and steam protective clothing.
REtrieving thrombi and Separated Coils/catheters Unexpectedly detached during Endovascular therapy: RESCUE – the use of thrombectomy devices for rescue therapy in interventional neuroradiology
Authors: Herlihy Darragh , Singh Sneha , Nicholson Patrick , Griffin Emma , O’Hare Alan , Brennan Paul , Thornton John , Power Sarah
Published: December 2024

Purpose

Intraprocedural complications during intracranial embolisation include thromboembolic vessel occlusion, catheter tip detachment and coil migration. Stentrievers and aspiration catheters are valuable devices for the management of these complications. We present our experience with the use of these devices. We describe the devices and techniques used, case details and clinical outcomes. Currently there is no standardised approach for the management of the above intraprocedural complications.

Methods

We performed a retrospective review of our interventional neuroradiology database of patients who underwent endovascular treatment in our institution from January 2012 to January 2019 and identified embolisation procedures during which either stentrievers or aspiration catheters were utilised.

Results

We present a case series of 24 cases in which these devices were utilised as rescue devices over a period of 7 years. We provide three illustrative cases.

Conclusion

Stentrievers and aspiration catheters can be used safely and effectively as adjunctive or rescue devices during embolisation procedures.
The relationship between social media use and pregnancy-related body image
Authors: Rosenbaum Diane L , Gillen Meghan M , Hutson David J
Published: December 2024

Background:

Social media negatively affects body image, but few have investigated its impact on pregnancy-related body image. Pregnancy represents a vulnerable period for body image, and poor body image has negative implications for health.

Objectives:

We aimed to (1) understand relations of social media and pregnancy-related body image variables, (2) examine differences in social media use and body image based on demographic characteristics, and (3) evaluate whether type of social media use (i.e., active versus passive) was differentially related with body image based on time spent on social media.

Design:

This was a cross-sectional study.

Methods:

We recruited an online sample of women ( N = 154) experiencing early motherhood, as defined by giving birth within the past 5 years. We examined social media use (e.g., amount of time, type of use) on Facebook, Instagram, and Twitter in relation to pregnancy-related body image questionnaires.

Results:

Passive use (e.g., viewing others’ content rather than creating original content) and greater time on Facebook were independently related to lower positive body image. Those who passively used Facebook for the longest amount of time had the lowest positive body image. No significant effects were found for Instagram or Twitter.

Conclusion:

Spending more time passively viewing others’ content may facilitate social comparison, reducing positive feelings about one’s own body. Social media may constitute a source of pressure and scrutiny for women, resulting in lowered pregnancy-related body image.
Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management
Authors: Bertin Luisa , Crepaldi Martina , Zanconato Miriana , Lorenzon Greta , Maniero Daria , de Barba Caterina , Bonazzi Erica , Facchin Sonia , Scarpa Marco , Ruffolo Cesare , Angriman Imerio , Buda Andrea , Zingone Fabiana , Barberio Brigida , Savarino Edoardo Vincenzo
Published: December 2024

Crohn’s disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD management. However, the path to developing new therapies for inflammatory bowel disease (IBD) is fraught with challenges, including complex trial designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape of IBD clinical trials is shifting toward greater inclusivity, improved patient diversity, and innovative trial designs, such as adaptive and Bayesian approaches, to address these challenges. By overcoming these obstacles, the drug development pipeline can advance more effective, accessible, and timely treatments for CD.
Immuno-combined treatment versus radio-combined treatment in limited-stage small-cell lung cancer
Authors: Tong Li , Li Xiaomi , Hu Mingming , Zhang Minghang , Wang Yishuo , Zhang Kai , Wang Qunhui , Zhang Tongmei , Li Baolan
Published: December 2024

Background:

Although the approval of immunotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) has significantly improved the patient’s prognosis, synchronous chemoradiotherapy has always been the standard treatment for limited-stage small-cell lung cancer (LS-SCLC).

Objectives:

Immuno-combined and radio-combined therapy in LS-SCLC has been applied in clinical practice, but what is the best for LS-SCLC?

Design:

This was a retrospective cohort study.

Methods:

Patients with LS-SCLC from January 2019 to December 2023 were retrospectively screened and divided into three groups according to the initial treatment regimen whether included immune-combined and radio-combined treatment. Univariate and multivariate Cox regression were used to analyze the predictors affecting the survival of LS-SCLC, and the progression pattern of patients and the occurrence of adverse events (AEs) were also recorded.

Results:

In this study, the median overall survival (OS) was 15.8 months, not yet reached (NR) and NR, and the median progression-free survival (PFS) was 11.7, 20.9, and 18.9 months in the immunotherapy combined chemotherapy ( N = 34), immune combined chemoradiotherapy ( N = 26), and chemoradiotherapy ( N = 53) groups, respectively. OS and PFS were significantly prolonged in the radio-combined groups compared with the non-radio-combined group, and there was no significant difference between the radio-combined groups, namely immunotherapy combined chemoradiotherapy and chemoradiotherapy groups. In this study, we also constructed some indexes to predict prognosis for LS-SCLC, derived neutrophil and lymphocyte ratios were significantly associated with worse survival, and systemic inflammatory index and neuron-specific enolase (NSE) levels were significantly associated with shorter PFS. The primary organs of progression remained the lung and brain, the main immune-related AE was hypothyroidism, and the radiation-related AE was pneumonia.

Conclusion:

Radiation-combined therapy still plays an important role in LS-SCLC in the era of immunotherapy, and clinicians cannot abandon the use of radiation therapy in the initial treatment plan for LS-SCLC.
Infrahyoid Myocutaneous Flaps with Common Wall of Hypopharyngeal and Esophageal Serosas for Voice Rehabilitation After Total Laryngectomy
Authors: Lu Zhiyan , Li Changjiang , Chen Jian , Shu Min , Wang Yimiao , Li Dan , Chen Siyi , Ma Shuaichi , Cheng Lei , Wu Haitao , He Peijie
Published: December 2024

Importance

Patients who undergo total laryngectomy lose the voice function permanently. It is important to reconstruct the voice function of the patients after total laryngectomy.

Objective

To explore a novel method for voice rehabilitation by suturing infrahyoid myocutaneous flaps to the hypopharyngeal and esophageal serosas after total laryngectomy and investigate its clinical efficacy.

Design

Clinical study (retrospective study).

Participants

Twenty patients with advanced laryngocarcinoma who underwent total laryngectomy.

Methods

Following total laryngectomy, the pharyngeal cavity was formed via layer-by-layer suturing, and the infrahyoid myocutaneous flap was sutured to the common wall of hypopharyngeal and esophageal serosas to create a voice tube.

Results

Flap failure was not observed in any patient. All patients were able to vocalize after surgery. The voice after the reconstruction was smooth and natural. However, 3 patients were unable to vocalize gradually. Two patients experienced aspiration, requiring the removal of the voice tube, while 3 patients exhibited mild aspiration, which could be overcome by pressing the larynx on the voice tube surface.

Conclusions

Using infrahyoid myocutaneous flaps with the common wall of the hypopharyngeal and esophageal serosas was effective in rehabilitating voice after total laryngectomy. Future clinical studies are necessary to validate the effectiveness of this technology for voice rehabilitation.
How people connect fairness and equity when they talk about data uses
Authors: Kennedy Helen , Ditchfield Hannah , Oman Susan , Bates Jo , Perea Itzelle Medina , Fratczak Monika , Taylor Mark
Published: December 2024

As a mechanism for addressing data-related harms, fairness has been subjected to considerable criticism, seen as failing to acknowledge the power relationships that produce said harms, or as a ‘floating signifier’ devoid of specific meaning. In contrast to fairness, it is argued that equity does a better job of recognising data-related harms. Criticisms such as these emerge in specific cultural contexts and rarely acknowledge everyday understandings of terms and concepts. This paper engages with these criticisms, drawing on research exploring how 112 UK residents perceive data uses in specific public service organisations. We found that participants perceive fairness and equity to be interwoven with each other, a finding which shows that who gets to define what is fair matters and which challenges assumptions about what does and does not constitute thinking and talking data politics. We conclude by proposing that linking fairness with equity can be seen as a kind of everyday data solidarity.
Service quality evaluation of integrated health and social care for older Chinese adults in residential settings based on factor analysis and machine learning
Authors: Liu Zhihan , Ouyang Caini , Gu Nian , Zhang Jiaheng , He Xiaojiao , Feng Qiuping , Chang Chunguyu
Published: December 2024

Objective

To evaluate the service quality of integrated health and social care institutions for older adults in residential settings in China, addressing a critical gap in the theoretical and empirical understanding of service quality assurance in this rapidly expanding sector.

Methods

This study employs three machine learning algorithms—Backpropagation Neural Networks (BPNN), Feedforward Neural Networks (FNN), and Support Vector Machines (SVM)—to train and validate an evaluative item system. Comparative indices such as Mean Squared Error, Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), and predictive performance metrics were employed to assess the models.

Results

The service quality evaluation model, enhanced by factor analysis and fuzzy BPNN, demonstrated reduced error rates and improved predictive performance metrics. Key factors influencing service quality included daily care, medical attention, recreational activities, rehabilitative services, and psychological well-being, listed in order of their impact.

Conclusion

The BPNN-based model provides a comprehensive and unified framework for assessing service quality in integrated care settings. Given the pressing need to match service supply with the complex demands of older adults, refining the service delivery architecture is essential for enhancing overall service quality.
Feasibility of using an artificially intelligent chatbot to increase access to information and sexual and reproductive health services
Authors: Bull Sheana , Hood Shakari , Mumby Sara , Hendrickson Anna , Silvasstar Joshva , Salyers Adam
Published: December 2024

Background

Following the US Supreme Court decision overturning Roe v. Wade, there is evidence of limitations in access to safe abortion care. Artificially intelligent (AI)-enabled conversational chatbots are becoming an appealing option to support access to care, but generative AI systems can misinform and hallucinate and risk reinforcing problematic bias and stigma related to sexual and reproductive healthcare.

Method

A single arm pilot study describing the development of an AI chatbot focused on sexual and reproductive health and its deployment in a clinic setting and community-based organization over a nine-month period.

Results

We adjusted chatbot content based on feedback from the medical director and clients of organizations where the system was deployed given updated medical guidelines and preferred language related to gender-affirming care. We deployed the system in two organizations and tracked use over nine months. In that time, there were 1749 queries from 425 unique users. One-tenth of users of the clinic based chatbot went on to schedule an appointment for care.

Conclusions

Ongoing challenges in accessing sexual and reproductive health suggest having diverse mechanisms to facilitate access to accurate and updated medical information is warranted. Using an AI chatbot is feasible to accomplish this goal and shows promise in increasing opportunities to access care.
#BookTok’s Peer Pedagogies: Invitations to Learn About Books and Reading on TikTok
Authors: Dezuanni Michael , Schoonens Amy
Published: December 2024

This article extends the idea of media pedagogies to consider how TikTok provides a site of social learning about books and reading. It uses the concept of “peer pedagogies” to identify how the #BookTok hashtag is used to invite book and reading enthusiasts to take up learning positions. The article uses an exploratory approach to identify contrasting videos in which learning about books and reading is made available, and it undertakes an in-depth content and semiotic analysis of three videos to consider how learning is framed in different ways. The article is informed by Bernstein’s theorization of pedagogical classification and framing, which relates to how knowledge and skills are institutionally defined, and how knowledge is made available along a continuum of greater and less formality. This approach enables a consideration of the learning positions available to members of the #BookTok community as they engage with the videos. The article shows how #BookTok creators make deliberate creative and pedagogical choices to use TikTok’s affordances to share knowledge and skills as a form of public media pedagogy and service to the #BookTok community. In addition, it argues that the sharing of knowledge and skills between people who share a passion and interest in books and reading contributes to the videos’ popularity and success.
Navigating “Promising Victimhood:” Discretionary Practices of UNHCR Caseworkers in Rwanda’s Refugee Resettlement Process
Authors: Bækkevold Kine Marie , Bjørkhaug Ingunn , Irankunda Jerome , Divon Shai André
Published: December 2024

Executive Summary

As the global refugee population continues to expand, resettlement opportunities remain scarce, accessible only to a select few. Scholarly literature has increasingly drawn attention to the opaque bureaucratic processes, often referred to as “black boxes,” that govern resettlement selection, revealing that the decision-making practices determining which refugees are chosen for resettlement are still not well understood. This study addresses a critical gap concerning the implementation of selection criteria within UNHCR’s operations in the Global South, with a specific focus on caseworkers in Rwanda. It examines how these criteria are applied in practice, providing new empirical insights into the concept of “promising victimhood” — the contradictory demands placed on refugees to simultaneously demonstrate both vulnerability and integration potential to qualify for asylum or resettlement. The study explores how caseworkers navigate their roles amidst the complex and often conflicting demands imposed on refugees during the selection process. The analysis is grounded in interviews with sixteen caseworkers involved in resettlement selection, employing street-level bureaucracy theory alongside the concepts of refugee deservingness and promising victimhood. As key actors in the selection process, caseworkers exercise bottom-up power as policy implementers, while simultaneously adhering to the top-down directives established by resettlement states. The findings reveal that caseworkers employ a range of discretionary practices to reconcile the demands of resettlement states’ admission criteria with their advocacy for refugees deemed most vulnerable by the UNHCR. This research enhances our understanding of UNHCR’s operations at the street level, shedding light on how the practices of caseworkers influence perceptions of refugee eligibility and ultimately influence who is granted resettlement.
HotBENT experiment on quality control of bentonites used for granular bentonite material backfilling and block production
Authors: Kaufhold Stephan , Dohrmann Reiner , Ufer Kristian , Gröger-Trampe Jens , Kober Florian , Schneeberger Raphael , Weber Christian
Published: December 2024

The maximum temperature that a geotechnical bentonite barrier in a deep geological repository for radioactive waste can withstand while maintaining its integrity and meeting safety requirements is still an open question. Therefore, an international consortium set up an in situ heater test (HotBENT experiment) at the Grimsel Test Site (GTS) in Switzerland at relevant scales and gradients with temperatures ranging from 175°C to 200°C at the heater/canister surface. After dismantling (5 and 20 years, respectively), the identification of bentonite alteration processes of (clay) minerals has to be based on the comparison of data with reference values determined before the heating started. The experiment was set up using ~150 tons of two different clays (Wyoming and BCV from the Czech Republic) provided in different batches. The bentonites were used both as compacted bentonite blocks and as granular bentonite material (GBM). The determination of representative mineralogical and geochemical bentonite reference values must be based on a significant number of samples taken from all parts of the experiment, which is presented here. Most of the compositional variability was close to the accuracy of the methods used. However, chemical, mineralogical and exchangeable cation analyses showed that different raw materials were used to produce the BCV top blocks. The Wyoming bentonite used is similar to MX80 bentonite in that it is dominated by Na-rich smectite, but the HotBENT material contains slightly more feldspar and zeolite and slightly less smectite. Overall, 55 samples were analysed from different parts of the experiment, providing a statistical basis for post-excavation investigations.
Approaching hypercalcemia in monoclonal gammopathy of undetermined significance: insights from the iStopMM screening study
Authors: Jónsdóttir Ástrún Helga , Sigurjónsdóttir Helga Ágústa , Thorsteinsdóttir Sigrun , Long Thorir Einarsson , Sverrisdóttir Ingigerður Sólveig , Eythorsson Elias , Óskarsson Jón Þórir , Palsson Runolfur , Indridason Olafur Skuli , Viðarsson Brynjar , Onundarson Pall Torfi , Ólafsson Ísleifur , Þorsteindóttir Ingunn , Agnarsson Bjarni A. , Sigurðardóttir Margrét , Jónsson Ásbjörn , Hultcrantz Malin , Durie Brian G. M. , Harding Stephen , Landgren Ola , Love Thorvardur Jon , Kristinsson Sigurður Yngvi , Rögnvaldsson Sæmundur
Published: December 2024

Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge because it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the Iceland Screens, Treats, or Prevents Multiple Myeloma screening study. Of the 75 422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2546 with MGUS who were in active follow-up, including regular serum calcium measurements. In total, 191 individuals (7.5%) had hypercalcemia detected at least once, of whom 93 had persistent hypercalcemia (48.7%). MM was found in 3 participants with persistent hypercalcemia (3.2%); all had concurrent bone disease and other end-organ damage. The most common causes of hypercalcemia were primary hyperparathyroidism (56.0%) and malignancies other than MM (16.0%). In this first comprehensive study on hypercalcemia in MGUS, we observed that hypercalcemia rarely indicated MGUS progression and never in the absence of other symptoms of MM. More than half of hypercalcemia cases were transient, and the underlying causes were similar to those in the general population. We conclude that hypercalcemia in MGUS should be approached in the same way as in those without MGUS.
How I treat quantitative fibrinogen disorders
Authors: Casini Alessandro
Published: December 2024

Quantitative fibrinogen disorders, including afibrinogenemia and hypofibrinogenemia, are defined by the complete absence or reduction of fibrinogen, respectively. The diagnosis is based on the measurement of fibrinogen activity and antigen levels, which define the severity of this monogenic disorder. Afibrinogenemia is the result of homozygosity or combined heterozygosity for the causative mutations, whereas monoallelic mutations lead to hypofibrinogenemia. The bleeding phenotype varies in accordance with fibrinogen levels, ranging generally from frequent and often life-threatening bleeding in afibrinogenemia to the absence of symptoms, or mild bleeding symptoms in mild hypofibrinogenemia. The main treatment for quantitative fibrinogen disorders is fibrinogen supplementation. Despite low fibrinogen levels, a tendency for thrombosis is a characteristic of these disorders and may be exacerbated by fibrinogen supplementation. The management of surgery and pregnancy presents significant challenges regarding the amount of fibrinogen replacement and the need for thromboprophylaxis. The objective of this article is to present 4 clinical scenarios that illustrate common clinical challenges and to propose strategies for managing bleeding, thrombosis, surgery, and pregnancy.
Space, time, and presence in video consultations: an interview study in Danish general practice
Authors: Kofod Frida Greek , Christensen Anne-Marie Søndergaard , Hvidt Elisabeth Assing , Arreskov Anne Beiter , Guassora Ann Dorrit
Published: December 2024

Background

The purpose of this interview study was to explore patients’ and general practitioners’ (GPs’) experiences of space, time, and presence in video consultation in general practice in Denmark.

Methods

The study included six GPs and seven patients from the Copenhagen area, with different experience of video consultations. The data consisted of semi-structured interviews with all participants including recordings from their video consultations. The transcribed interviews were analyzed by Interpretative Phenomenological Analysis (IPA). The theoretical analysis was inspired by philosopher K.E. Løgstrup’s writings about time, space, presence and sensation.

Results

Both the patients and the GPs experienced a lack, or a different form, of presence in video consultations, comparing it to face-to-face consultations. Patients felt more secure in their own homes and the GPs found some of them to be more relaxed during the video consultation than in the face-to-face consultation taking place in the surgery. However, the consultation felt more superficial, with the GPs and patients experiencing an alteration in their sensory access to one another. The video consultation was also perceived as purpose-driven and action-oriented.

Both patients and GPs felt that time was saved. According to K.E. Løgstrup, our experience is always composed of spatiality and temporality; the space is where we sense one another and experience duration, while time is the awareness of change and action. The theoretical analysis points to the experience of presence as spatial and, owing to the changed space in video consultations, the experience of presence and time is changed.

Conclusion and Implications

The balance between space and time is altered in the video consultation. GPs and patients lack certain sensory impressions, owing to the changed spatiality. The changed spatiality, sensation and experiences of presence lead the participants to eliminate the expendable elements to make the consultation more efficient.

Video consultations allow some issues to be handled quickly, but the option for physical consultations still needs to be available, as we believe we now can argue that the physical consultation room has importance for the experience of presence and time.
Factors associated with functional health literacy and the quality of life of riverside residents served by the primary care network in the Brazilian amazon: a cross-sectional study
Authors: Pinheiro Ana Kedma Correa , Raymundo Carlos Eduardo , da Silva Santos Eliene do Socorro , Saldanha dos Santos Marcio Yrochy , de Oliveira Sarefino Adriana , do Nascimento Souza Maria Helena , Lima Ingrid Bentes , da Silva Raquel Gomes , Nogueira Laura Maria Vidal
Published: December 2024

Background

the riverside population lives in a vulnerable social situation, shaped by geographical, economic, social, and educational aspects that have repercussions on health literacy, the limitations of which can compromise Quality of Life. These specificities influence the actions of Primary Health Care, especially in the rural context. This study aimed to assess the factors associated with Functional Health Literacy and Quality of Life among riverside residents of the Brazilian Amazon who use Primary Health Care.

Methods

a cross-sectional study with 312 users of a riverside Family Health Team, using the Health Literacy Test, classified as adequate, limited, and inadequate, and the Study Short Form 12 Health Survey questionnaire, analyzing the physical and mental components in isolation. A theoretical model was built to assess the associations between sociodemographic and environmental variables and the Functional Health Literacy and Quality of Life outcomes. The Functional Health Literacy outcome was considered as two dichotomous variables (inadequate versus adequate; limited versus adequate), while the Quality of Life outcomes were considered as counts, with a Poisson distribution. Thus, a structural equation model was used to adjust the proposed theoretical model.

Results

there was a worsening in inadequate Functional Health Literacy, associated with females, aged over 40, elementary school education, living close to the health service, and using only a cell phone for communication. Factors that compromised physical Quality of Life: livelihood problems; inadequate literacy; age range 40–59; and having two children or more. And those that worsened mental Quality of Life: age over 40; having a family allowance; and being in control of their medication.

Conclusions

sociodemographic, environmental, and economic factors and adherence to medication by river communities have been shown to be associated with Health Literacy and Quality of Life. Knowing these implications is fundamental for health provision. These findings can support the formulation of strategies in health services to improve Health Literacy and Quality of Life.
Implementation and sustainment of virtual reality stroke workflow training for physician trainees at comprehensive stroke centres: a quantitative and qualitative study
Authors: Maltby Steven , Mahadevan Joshua J. , Spratt Neil J. , Garcia-Esperon Carlos , Kluge Murielle G. , Paul Christine L. , Kleinig Timothy J. , Levi Christopher R. , Walker Frederick R.
Published: December 2024

Background

Variation in stroke treatment metrics highlight a need for approaches to improve clinical processes. Training interventions can improve outcomes, but Australian physician trainees do not currently receive formal process-directed stroke training. Virtual reality (VR) stroke workflow training has proven acceptable, usable, useful and feasible in trial contexts, but how to integrate VR training into physician training remains unclear. The current study sought to document stroke staff perceptions of existing training and assess implementation of routine VR training at comprehensive stroke centres, outside of a trial context.

Methods

Training was delivered to physician trainees via individual sessions or facilitated group workshops depending on the hospital site. VR usage data was captured automatically via Wi-Fi. Survey responses from both trainees and training staff were collected, with statistical comparisons performed for matching questions in pre- and post-training surveys. Themes identified in open-ended survey responses were enumerated and reported.

Results

Forty-two TACTICS VR training sessions were logged at 2 hospitals between May 2022 and October 2023. Trainees reported receiving low amounts of prior formal stroke training; both trainees and training staff identified unmet needs and barriers to existing training. VR users (n = 30) provided positive feedback on VR hardware, software design, user experience, content, educational value and delivery approach (mean scores 3.9 to 4.7; 1 = strongly disagree, 5 = strongly agree). VR training improved confidence in: knowledge of acute stroke assessment / treatment (post-training vs. pre-training = 4.0±0.7 vs. 2.9±1.0; P < .0001), ability to effectively assess / treat stroke (4.0±0.6 vs. 3.1±1.0; P < .0001), ability to optimally communicate with colleagues (4.1±0.6 vs. 3.3±1.0; P < .001), understanding of workflow practices (4.3±0.6 vs. 3.2±1.2; P < .0001), ability to make improvements (4.1±0.8 vs. 3.0±1.2; P < .0001) and awareness of local stroke management criteria / processes (4.1±0.8 vs. 3.6±1.1; P < .01). Respondents suggested enhancements in funding, access, awareness, training populations and delivery modality to improve training sustainment.

Conclusions

VR stroke workflow training was perceived by trainees and training staff as feasible, acceptable, usable, useful and positively impacted stroke training. Respondents endorsed future use of VR training to support training at comprehensive stroke centres and identified aspects for improved future integration.
In vitro and in vivo studies of selenium nanoparticles coated bacterial polysaccharide as anti-lung cancer agents
Authors: Shehata Nourhan S. , Elwakil Bassma H. , Elshewemi Salma S. , Ghareeb Doaa A. , Olama Zakia A.
Published: December 2024

Microbial exopolysaccharides (EPSs) possess valuable biological functions and fascinating physicochemical properties. On the other hand, lung cancer is the primary contributor to global cancer-related deaths. However, health and safety concerns have prevented the identification and approval of any medications, including chemotherapeutic agents, for lung cancer treatment to date. The current study aims to enhance the production of bacterial EPS as a coating agent for the synthesis of selenium nanoparticles (AZEPS-SeNPs), to enhance their biological activity against pathogenic microbes, human lung adenocarcinoma cells (A549) in vitro, and diethyl nitrosamine (DEN)-induced lung cancer in vivo. The synthesized AZEPS-SeNPs exhibited a significant antifungal effect reaching 49.3 mm against Candida albicans. SeNPs and EPSs demonstrated a concentration-dependent synergistic antioxidant effect of 96.8%. Moreover, the synthesized nanoparticles showed a highly potent cytotoxic effect against A549 cells (1.724 ± 0.08 µg/mL) with a therapeutic index of 7.18 ± 0.21 that leads to increased reactive oxygen species (ROS) production. AZEPS-SeNPs demonstrated a proapoptotic effect on the lung adenocarcinoma A549 cell line by stimulating caspase 3 and Bax (7.08-fold and 6.505-fold, respectively), inhibiting the anti-apoptotic gene Bcl2, and arresting the cell cycle in the S phase. In vivo study revealed that the AZEPS-SeNPs-treated group showed improved histopathological examination of lung tissue sections. The present study concluded the efficiency of the synthesized bacterial EPS-SeNPs as multi-functional antimicrobial, anticancer and antioxidant agent.
Development of a prognostic model based on lysosome-related genes for ovarian cancer: insights into tumor microenvironment, mutation patterns, and personalized treatment strategies
Authors: Sun Ran , Li Siyi , Ye Wanlu , Lu Yanming
Published: December 2024

Background

Ovarian cancer (OC) is often associated with an unfavorable prognosis. Given the crucial involvement of lysosomes in tumor advancement, lysosome-related genes (LRGs) hold promise as potential therapeutic targets.

Methods

To identify differentially expressed lysosome-related genes (DE-LRGs), we performed a matching analysis between differentially expressed genes (DEGs) in OC and the pool of LRGs. Genes with prognostic significance were analyzed using multiple regression analyses to construct a prognostic risk signature. The model's efficacy was validated through survival analysis in various cohorts. We further explored the model's correlation with clinical attributes, tumor microenvironment (TME), mutational patterns, and drug sensitivity. The quantitative real-time polymerase chain reaction (qRT-PCR) validated gene expression in OC cells.

Results

A 10-gene prognostic risk signature was established. Survival analysis confirmed its predictive accuracy across cohorts. The signature served as an independent prognostic element for OC. The high-risk and low-risk groups demonstrated notable disparities in terms of immune infiltration patterns, mutational characteristics, and sensitivity to therapeutic agents. The qRT-PCR results corroborated and validated the findings obtained from the bioinformatic analyses.

Conclusions

We devised a 10-LRG prognostic model linked to TME, offering insights for tailored OC treatments.
Mechanical stability of the proximal tibia with different bone formations after plate removal in medial opening-wedge high tibial osteotomy: a finite element analysis
Authors: Jang Chul-Young , Kang Kyoung-Tak , Hong Hyongtaek , Jung Min , Kim Sungjun , Yoo Je-Hyun , Kim Sung-Hwan
Published: December 2024

Background

No clear agreement exists on the degree of bone formation required to remove a metal plate without correction loss after medial opening-wedge high tibial osteotomy (MOWHTO). We aimed to investigate the mechanical stability of the proximal tibia with different bone formations after plate removal in MOWHTO using finite element models and determine the extent of bone formation when the plate can be removed without correction loss.

Methods

The MOWHTO models with 5, 10, and 15 mm opening gaps were generated. The mechanical stability of proximal tibial models with different extents of bone formation (from the lateral cortex of the osteotomy wedge to 20% (zone 1), 40% (zone 2), 50% (zone 2.5), 60% (zone 3), 70% (zone 3.5), 80% (zone 4), and 100% bone formation medially) after plate removal was analyzed using finite element analysis. Bone stress and strain and micromotion were evaluated to investigate fracture risk and bone stability, respectively, in various types of tibial models.

Results

Peak von Mises stress was lower than yield strength when bone formation reached zone 3.5 (70%) or more in 5- and 10-mm osteotomy gap models, and zone 4 (80%) or more in a 15-mm gap model. Maximal principal strains were lower than 6,130 microstrain when bone formation reaches zone 3.5 (70%) or more in models with osteotomy gaps of 5, 10, and 15 mm.

Conclusions

This indicates that plate removal without correction loss after MOWHTO may be possible when bone formation reaches zone 3.5 (> 70%) or more during 5- and 10-mm osteotomy gap corrections, and zone 4 (> 80%) or more during 15-mm gap correction. The present study results suggest that it would be safer to perform plate removal after obtaining sufficient bone formation rather than performing it near the osteotomy gap center (50%) to avoid correction loss considering both coronal and sagittal plane aspects.
Microscopy observations reveal a new glandular morphology in four Pinguicula L. species
Authors: Natale Sara , Canella Marco , Moschin Silvia , Baldan Barbara , Alboresi Alessandro , La Rocca Nicoletta , Dal Grande Francesco
Published: December 2024

The adaxial leaf surface of butterworts (Pinguicula L.) presents specialized structures for carnivory, such as trichomes and sessile glands. The micromorphology of abaxial leaf surfaces has rarely been investigated; therefore, this study aimed to compare the micromorphology of adaxial and abaxial surfaces through electron scanning microscopy (SEM) and light microscopy (LM). We selected four species occurring in the Eastern Alps. All the species showed the same pattern: trichomes and sessile glands occurring only on the adaxial surface; stomata occurring on both surfaces with significant differences in density and size; and four-cells glands occurring only on the abaxial surface. The four-cells gland is a micromorphological structure that has never been described before, and its eco-physiological function needs to be investigated.
Response to Schmidt et al.: Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis
Authors: Anderson Emma L
Published: December 2024

A recent paper concluded that cholesteryl ester transfer protein (CETP) inhibition may be a viable target to treat dementia, based on human genetic evidence of a protective effect of target inhibition on risk of Lewy body and Parkinson’s dementia. Alzheimer’s disease, which is by far the most prevalent cause of dementia (around 80% of all dementia cases) was not included as an outcome. Evidence shows CETP inhibition is unlikely to affect Alzheimer’s risk and may even potentially modestly increase risk. There is also little evidence to support an effect of CETP inhibition on all-cause or vascular dementia. Thus, CETP inhibition is unlikely to be a viable target to treat the most prevalent causes of dementia.
Unmasking culprits: novel analysis identifies complement factors as potential therapeutic targets to mitigate inflammation during children's heart surgery
Authors: Bierer Joel , Stanzel Roger , Henderson Mark , Sapp John , Andreou Pantelis , Marshall Jean S. , Horne David
Published: December 2024

Background

Cardiopulmonary bypass (CPB) causes systemic inflammation during pediatric cardiac surgery, which can contribute to post-operative organ dysfunction and prolonged recovery. This study aims to identify key inflammatory mediators related to this clinically significant immunologic response.

Methods

Pediatric patients were enrolled in a single-arm prospective clinical study (NCT05154864) and received standard cardiac operation, CPB and subzero-balance ultrafiltration. Arterial samples were taken before CPB initiation and immediately after weaning, and concentrations of 33 inflammatory mediators were assayed. A principal component analysis with hierarchical clustering (PCA-HCPC) included inflammatory mediator concentrations measured at the end of CPB, validated peak post-operative clinical scores, ventilation time and intensive care length of stay. Mahalanobis distance assessed statistical differences between clusters. Spearman’s correlation described the linear relationship between mediator concentrations at the end of CPB and intensive care length of stay. Results are median (IQR).

Results

Forty consecutive patients were enrolled; the majority were male (58%), age of 7.3 (1.7–39.0) months and weight of 6.7 (4.6–14.9) kg. The PCA-HCPC revealed activated complement factors along with all peak clinical scores and prolonged intensive care requirements in the same cluster. Cytokine, chemokine, and leukocyte adhesion molecule concentrations were found in two other distinct clusters (Mahalanobis distance = 16.5; p = 0.004 and Mahalanobis distance = 17.4; p = 5.8 × 10–4). Mediator concentrations of C2 (Rho = 0.50; p = 0.001), C3 (Rho = 0.58; p = 1.1 × 10–4), C3b (Rho = 0.47; p = 0.002), C5 (Rho = 0.48; p = 0.002) and C5a (Rho = 0.63; 1.7 × 10–5) showed linear correlations with intensive care unit length of stay.

Conclusions

Activated complement factors, but not pro-inflammatory cytokines or chemokines, were most related to cardiopulmonary dysfunction and prolonged recovery in this novel analysis. Investigation of therapies that inhibit complement to dampen CPB-associated inflammation and enhance recovery after pediatric cardiac surgery is warranted.

Trial Registration ClinicalTrials.gov, NCT05154864
CD2AP deficiency aggravates Alzheimer’s disease phenotypes and pathology through p38 MAPK activation
Authors: Xue Yan-Yan , Zhang Zhe-Sheng , Lin Rong-Rong , Huang Hui-Fen , Zhu Ke-Qing , Chen Dian-Fu , Wu Zhi-Ying , Tao Qing-Qing
Published: December 2024

Background

Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder, which is characterized by a decline in cognitive abilities. Genome-wide association and clinicopathological studies have demonstrated that the CD2-associated protein (CD2AP) gene is one of the most important genetic risk factors for AD. However, the precise mechanisms by which CD2AP is linked to AD pathogenesis remain unclear.

Methods

The spatiotemporal expression pattern of CD2AP was determined. Then, we generated and characterized an APP/PS1 mouse model with neuron-specific Cd2ap deletion, using immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay, electrophysiology and behavioral tests. Additionally, we established a stable CD2AP-knockdown SH-SY5Y cell line to further elucidate the specific molecular mechanisms by which CD2AP contributes to AD pathogenesis. Finally, the APP/PS1 mice with neuron-specific Cd2ap deletion were treated with an inhibitor targeting the pathway identified above to further validate our findings.

Results

CD2AP is widely expressed in various regions of the mouse brain, with predominant expression in neurons and vascular endothelial cells. In APP/PS1 mice, neuronal knockout of Cd2ap significantly aggravated tau pathology, synaptic impairments and cognitive deficits. Mechanistically, the knockout of Cd2ap activated p38 mitogen-activated protein kinase (MAPK) signaling, which contributed to increased tau phosphorylation, synaptic injury, neuronal apoptosis and cognitive impairment. Furthermore, the phenotypes of neuronal Cd2ap knockout were ameliorated by a p38 MAPK inhibitor.

Conclusion

Our study presents the first in vivo evidence that CD2AP deficiency exacerbates the phenotypes and pathology of AD through the p38 MAPK pathway, identifying CD2AP/p38 MAPK as promising therapeutic targets for AD.
A schedule for phasing-out knife crime
Authors: Farrell Graham , Davies Toby
Published: December 2024

Knife crime has become a prominent and seemingly intractable problem in England & Wales. Theory and evidence indicate that reducing crime opportunities is an effective means of crime control, including restrictions on lethal weapons. While public debate has centred on zombie and other ‘status’ knives, the most prevalent homicide weapon is a kitchen knife. Here we argue that replacing lethal pointed-tip kitchen knives with safer round-tip knives would reduce knife crime with little or no displacement. Drawing on the approach to remove fossil-fuel vehicles from roads, we propose a phased removal of lethal kitchen knives that we estimate will cut knife-related homicide in half, reduce other knife crime and criminality, and prevent thousands of non-criminal knife-related injuries.
Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses
Authors: Kim Myung Sup , Kang Hyeokgu , Baek Jung-Hwan , Cho Moon-Gyu , Chung Eun Joo , Kim Seok-Jun , Chung Joon-Yong , Chun Kyung-Hee
Published: December 2024

Background

Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Methods

In this work, we constructed conditional Hes1 knockout mice to selectively delete Hes1 in TAMs. We further analyzed the TME composition, T cell infiltration and activation, and anti-tumor effects in these mice, both alone and in combination with PD-1 checkpoint blockade.

Results

Our study showed that expression levels of Notch target Hes1 were increase in TAMs and mice with conditional knockout of Hes1 gene in TAMs exhibited decreased tumor growth, with increased infiltration and activation of cytotoxic T cells in tumors. Expression of tumor promoting factors was critically altered in Hes1-conditional KO TAMs, leading to the improved tumor microenvironment. Notably, arginase-1 expression was decreased in Hes1-conditional KO mice. Arg1 is known to deplete arginine and deactivate T cells in the TME. Administration of anti-PD-1 monoclonal antibody inhibited tumor growth to a greater extent in Hes1-conditional KO mice than in WT mice.

Conclusions

We identified a pivotal role for the Notch signaling pathway in shaping TAM function, suggesting that T-cell dysfunction in the TME is caused when the Notch target, HES1, in TAMs is upregulated by tumor-associated factors (TAFs), which, in turn, increases the expression of arginase-1. Targeting HES1 in TAMs appears to be a promising strategy for cancer immunotherapy.