bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma
Authors: Chen Wenqiong , He Yi , Zhou Guowei , Chen Xiang , Ye Youqiong , Zhang Guanxiong , Liu Hong
Published: January 2024

Background

Pyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one of the most commonly used models for immunotherapy development, though an inadequate immune response can occur. Moreover, the development of pyroptosis-related therapy and combinations with other therapeutic strategies is limited due to insufficient understanding of the role of pyroptosis in the context of different tumor immune microenvironments (TMEs).

Methods

Here, we present a computational model (pyroptosis-related gene score, PScore) to assess the pyroptosis status. We applied PScore to 1388 melanoma samples in our in-house cohort and eight other publicly available independent cohorts and then calculated its prognostic power of and potential as a predictive marker of immunotherapy efficacy. Furthermore, we performed association analysis for PScore and the characteristics of the TME by using bulk, single-cell, and spatial transcriptomics and assessed the association of PScore with mutation status, which contributes to targeted therapy.

Results

Pyroptosis-related genes (PRGs) showed distinct expression patterns and prognostic predictive ability in melanoma. Most PRGs were associated with better survival in metastatic melanoma. Our PScore model based on genes associated with prognosis exhibits robust performance in survival prediction in multiple metastatic melanoma cohorts. We also found PScore to be associated withBRAFmutation and correlate positively with multiple molecular signatures, such as KRAS signaling and the IFN gamma response pathway. Based on our data, melanoma with an immune-enriched TME had a higher PScore than melanoma with an immune-depleted or fibrotic TME. Additionally, monocytes had the highest PScore and malignant cells and fibroblasts the lowest PScore based on single-cell and spatial transcriptome analyses. Finally, a higher PScore was associated with better therapeutic efficacy of immune checkpoint blockade, suggesting the potential of pyroptosis to serve as a marker of immunotherapy response.

Conclusions

Collectively, our findings indicate that pyroptosis is a prognostic factor and is associated with the immune response in metastatic melanoma, as based on multiomics data. Our results provide a theoretical basis for drug combination and reveal potential immunotherapy response markers.
Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke
Authors: Gao Xin , Zhao Xinyi , Li Jiacheng , Liu Chang , Li Wenqiang , Zhao Junjie , Li Zhixi , Wang Nan , Wang Fang , Dong Jiawei , Yan Xiuwei , Zhang Jiheng , Hu Xueyan , Jin Jiaqi , Mang Ge , Ma Ruishuang , Hu Shaoshan
Published: January 2024

Aims

Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process.

Methods

As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients’ blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs.

Results

A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients’ neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model.

Conclusions

NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS.
Systematic assessment of chemokine ligand bias at the human chemokine receptor CXCR2 indicates G protein bias over β-arrestin recruitment and receptor internalization
Authors: Boon Katrijn , Vanalken Nathan , Szpakowska Martyna , Chevigné Andy , Schols Dominique , Van Loy Tom
Published: January 2024

Background

The human CXC chemokine receptor 2 (CXCR2) is a G protein-coupled receptor (GPCR) interacting with multiple chemokines (i.e., CXC chemokine ligands CXCL1-3 and CXCL5-8). It is involved in inflammatory diseases as well as cancer. Consequently, much effort is put into the identification of CXCR2 targeting drugs. Fundamental research regarding CXCR2 signaling is mainly focused on CXCL8 (IL-8), which is the first and best described high-affinity ligand for CXCR2. Much less is known about CXCR2 activation induced by other chemokines and it remains to be determined to what extent potential ligand bias exists within this signaling system. This insight might be important to unlock new opportunities in therapeutic targeting of CXCR2.

Methods

Ligand binding was determined in a competition binding assay using labeled CXCL8. Activation of the ELR + chemokine-induced CXCR2 signaling pathways, including G protein activation, β-arrestin1/2 recruitment, and receptor internalization, were quantified using NanoBRET-based techniques. Ligand bias within and between these pathways was subsequently investigated by ligand bias calculations, with CXCL8 as the reference CXCR2 ligand. Statistical significance was tested through a one-way ANOVA followed by Dunnett’s multiple comparisons test.

Results

All chemokines (CXCL1-3 and CXCL5-8) were able to displace CXCL8 from CXCR2 with high affinity and activated the same panel of G protein subtypes (Gαi1, Gαi2, Gαi3, GαoA, GαoB, and Gα15) without any statistically significant ligand bias towards any one type of G protein. Compared to CXCL8, all other chemokines were less potent in β-arrestin1 and -2 recruitment and receptor internalization while equivalently activating G proteins, indicating a G protein activation bias for CXCL1,-2,-3,-5,-6 and CXCL7. Lastly, with CXCL8 used as reference ligand, CXCL2 and CXCL6 showed ligand bias towards β-arrestin1/2 recruitment compared to receptor internalization.

Conclusion

This study presents an in-depth analysis of signaling bias upon CXCR2 stimulation by its chemokine ligands. Using CXCL8 as a reference ligand for bias index calculations, no ligand bias was observed between chemokines with respect to activation of separate G proteins subtypes or recruitment of β-arrestin1/2 subtypes, respectively. However, compared to β-arrestin recruitment and receptor internalization, CXCL1-3 and CXCL5-7 were biased towards G protein activation when CXCL8 was used as reference ligand.
Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome
Authors: Hartmannsberger Beate , Scriba Sabrina , Guidolin Carolina , Becker Juliane , Mehling Katharina , Doppler Kathrin , Sommer Claudia , Rittner Heike L.
Published: January 2024

Background

Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.

Methods

We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.

Results

Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.

Conclusions

Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.
Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration
Authors: Roubeix Christophe , Nous Caroline , Augustin Sébastien , Ronning Kaitryn E. , Mathis Thibaud , Blond Frédéric , Lagouge-Roussey Pauline , Crespo-Garcia Sergio , Sullivan Patrick M. , Gautier Emmanuel L. , Reichhart Nadine , Sahel José-Alain , Burns Marie E. , Paques Michel , Sørensen Torben Lykke , Strauss Olaf , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian
Published: January 2024

Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.
Conducting co-creation for public health in low and middle-income countries: a systematic review and key informant perspectives on implementation barriers and facilitators
Authors: Longworth Giuliana Raffaella , Erikowa-Orighoye Oritseweyinmi , Anieto Ebuka Miracle , Agnello Danielle Marie , Zapata-Restrepo Jorge Raul , Masquillier Caroline , Giné-Garriga Maria
Published: January 2024

Background

There has been an increase in the use of co-creation for public health because of its claimed potential to increase an intervention’s impact, spark change and co-create knowledge. Still, little is reported on its use in low-and-middle-income countries (LMICs). This study offers a comprehensive overview of co-creation used in public-health-related interventions, including the interventions’ characteristics, and reported implementation barriers and facilitators.

Methods

We conducted a systematic review within the Scopus and PubMed databases, a Google Scholar search, and a manual search in two grey literature databases related to participatory research. We further conducted eight interviews with first authors, randomly selected from included studies, to validate and enrich the systematic review findings.

Results

Through our review, we identified a total of twenty-two studies conducted in twenty-four LMIC countries. Majority of the interventions were designed directly within the LMIC setting. Aside from one, all studies were published between 2019 and 2023. Most studies adopted a co-creation approach, while some reported on the use of co-production, co-design, and co-development, combined either with community-based participatory research, participatory action research or citizen science. Among the most reported implementation barriers, we found the challenge of understanding and accounting for systemic conditions, such as the individual’s socioeconomic status and concerns related to funding constraints and length of the process. Several studies described the importance of creating a safe space, relying on local resources, and involving existing stakeholders in the process from the development stage throughout, including future and potential implementors. High relevance was also given to the performance of a contextual and/or needs assessment and careful tailoring of strategies and methods.

Conclusion

This study provides a systematic overview of previously conducted studies and of reported implementation barriers and facilitators. It identifies implementation barriers such as the setting’s systemic conditions, the socioeconomic status and funding constrains along with facilitators such as the involvement of local stakeholders and future implementors throughout, the tailoring of the process to the population of interest and participants and contextual assessment. By incorporating review and interview findings, the study aims to provide practical insights and recommendations for guiding future research and policy.
Development and validation of multiple linear regression models for predicting total hip arthroplasty acetabular prosthesis
Authors: Zou Ze-hui , Liu Xu-qiang , Li Wei-hua , Zhou Xin-tao , Li Xiao-feng
Published: January 2024

Purpose

To establish a multivariate linear equation to predict the diameter (outer diameter) of the acetabular prosthesis used in total hip arthroplasty.

Methods

A cohort of 258 individuals who underwent THA at our medical facility were included in this study. The independent variables encompassed the patients' height, weight, foot length, gender, age, and surgical access. The dependent variable in this study was the diameter of the acetabular prosthesis utilized during the surgical procedure. The entire cohort dataset was randomly partitioned into a training cohort and a validation cohort, with a ratio of 7:3, employing the SPSS 26.0 software. Pearson correlation analysis was conducted to examine the relationships between the patients' height, weight, foot length, gender, age, surgical access, and the diameter of the acetabular prosthesis in the training cohort. Additionally, a multiple linear regression equation was developed using the independent variables from the training cohort and the diameter of the acetabular prosthesis as the dependent variable. This equation aimed to predict the diameter of the acetabular prosthesis based on the patients' characteristics. The accuracy of the equation was evaluated by substituting the data of the validation cohort into the multiple linear equation. The predicted acetabular prosthesis diameters were then compared with the actual diameters used in the operation.

Results

The correlation analysis conducted on the training cohort revealed that surgical access (r = 0.054) and age (r = −0.120) exhibited no significant correlation with the diameter of the acetabular prosthesis utilized during the intraoperative procedure. Conversely, height (r = 0.687), weight (r = 0.654), foot length (r = 0.687), and sex (r = 0.354) demonstrated a significant correlation with the diameter of the acetabular prosthesis used intraoperatively. Furthermore, a predictive equation, denoted as Y (acetabular prosthesis diameter in mm) = 20.592 + 0.548 × foot length (cm) + 0.083 × height (cm) + 0.077 × weight (kg), was derived. This equation accurately predicted the diameter within one size with an accuracy rate of 64.94% and within two sizes with an accuracy rate of 94.81%.

Conclusion

Anthropometric data can accurately predict the diameter of acetabular prosthesis during total hip arthroplasty.
An exploration of the Indonesian lay mental health workers’ (cadres) experiences in performing their roles in community mental health services: a qualitative study
Authors: Susanti Herni , Brooks Helen , Yulia Ice , Windarwati Heni D. , Yuliastuti Estin , Hasniah Hasniah , Keliat Budi A.
Published: January 2024

Background

Volunteers trained to support community mental health programs in Indonesia are known as ‘mental health cadres.’ These are lay people trained to provide basic support for people with mental illness in their local communities. The role of cadres in community mental health services is to provide health promotion activities and support for people with mental illness, such as home visits and family assistance. Their contribution can potentially address the challenges health services currently face in remote and resource-limited settings. However, little is currently known about implementing this form of the lay workforce and the experiences of mental health cadres in Indonesia in particular. This study aimed to explore the experience of cadres when performing their roles in community mental health services in Indonesia from the cadres’ perspective.

Methods

The study employed a descriptive qualitative design. Purposive sampling was employed to recruit cadres with at least one year of experience handling those diagnosed with schizophrenia across four geographical areas in Java and Sumatra, Indonesia. Data were collected utilising focus groups undertaken between July and November 2020. Due to COVID-19 restrictions, eight focus group sessions for mental health cadres were carried out virtually via Zoom and non-virtual, facilitated by local moderators. Data were analysed using thematic analysis.

Results

The study involved 71 cadres in four regions: Aceh, Jakarta, West Java and East Java. The majority of participants were looking after their families with a minimum of high school-level qualifications. Four themes were interpreted from the data: (1) Motivation for volunteering, (2) The role of cadres in supporting mental health services, (3) Training and support needs in carrying out cadre roles, and (4) Barriers and facilitators to the implementation of cadre roles in local communities.

Conclusions

Cadres reported a motivation to help people improve their mental health and reduce the stigma associated with mental illness. Cadres also contributed to secondary and primary prevention of mental illness with some limitations. This study’s results are relevant to those wishing to understand and optimise the implementation of lay workforces in resource-limited settings.
PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1
Authors: Zheng Yuanliang , Zhang Lixiang , Zhang Kangliang , Wu Shenghao , Wang Chichao , Huang Risheng , Liao Hongli
Published: January 2024

Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression Omnibus (GEO) datasets that contain RNA sequencing data from ARID1A-depleted cancer cells. PLAU was identified as a common gene that was induced in different cancer cells upon ARID1A depletion. Overexpression of PLAU positively modulated NSCLC cell growth, colony formation, cisplatin resistance, and survival under serum deprivation. Moreover, enforced expression of PLAU enhanced tumorigenesis of NSCLC cells in nude mice. Mechanistically, PLAU interacted with TM4SF1 to promote the activation of Akt signaling. TM4SF1-overexpressing NSCLC cells resembled those with PLAU overepxression. Knockdown of TM4SF1 inhibited the growth and survival and increased cisplatin sensitivity in NSCLC cells. The interaction between PLAU and TM4SF1 led to the activation of Akt signaling that endowed ARID1A-depleted NSCLC cells with aggressive properties. In addition, treatment with anti-TM4SF1 neutralizing antibody reduced the growth, cisplatin resistance, and tumorigenesis of ARID1A-depleted NSCLC cells. Taken together, PLAU serves as a target gene of ARID1A and promotes NSCLC growth, survival, and cisplatin resistance by stabilizing TM4SF1. Targeting TM4SF1 may be a promising therapeutic strategy for ARID1A-mutated NSCLC.
Statistical analysis plan for a cluster randomised controlled trial to compare screening, feedback and intervention for child anxiety problems to usual school practice: identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i)
Authors: Ball Susan , Reardon Tessa , Creswell Cathy , Taylor Lucy , Brown Paul , Ford Tamsin , Gray Alastair , Hill Claire , Jasper Bec , Larkin Michael , Macdonald Ian , Morgan Fran , Pollard Jack , Sancho Michelle , Sniehotta Falko F. , Spence Susan H. , Stainer Jason , Stallard Paul , Violato Mara , Ukoumunne Obioha C.
Published: January 2024

Background

The Identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i) trial is being conducted to establish whether ‘screening and intervention’, consisting of usual school practice plus a pathway comprising screening, feedback and a brief parent-led online intervention (OSI: Online Support and Intervention for child anxiety), bring clinical and health economic benefits compared to usual school practice and assessment only — ‘usual school practice’, for children aged 8–9 years in the following: (1) the ‘target population’, who initially screen positive for anxiety problems according to a two-item parent-report child anxiety questionnaire — iCATS-2, and (2) the ‘total population’, comprising all children in participating classes. This article describes the detailed statistical analysis plan for the trial.

Methods and design

iCATS-i2i is a definitive, superiority, pragmatic, school-based cluster randomised controlled trial (with internal pilot), with two parallel groups. Schools are randomised 1:1 to receive either screening and intervention or usual school practice. This article describes the following: trial objectives and outcomes; statistical analysis principles, including detailed estimand information necessary for aligning trial objectives, conduct, analyses and interpretation when there are different analysis populations and outcome measures to be considered; and planned main analyses, sensitivity and additional analyses.

Trial registration

ClinicalTrials.gov ISRCTN76119074. Registered on 4 January 2022
Intratumoral and peritumoral CT radiomics in predicting prognosis in patients with chondrosarcoma: a multicenter study
Authors: Li Qiyuan , Wang Ning , Wang Yanmei , Li Xiaoli , Su Qiushi , Zhang Jing , Zhao Xia , Dai Zhengjun , Wang Yao , Sun Li , Xing Xuxiao , Yang Guangjie , Gao Chuanping , Nie Pei
Published: January 2024

Objective

To evaluate the efficacy of the CT-based intratumoral, peritumoral, and combined radiomics signatures in predicting progression-free survival (PFS) of patients with chondrosarcoma (CS).

Methods

In this study, patients diagnosed with CS between January 2009 and January 2022 were retrospectively screened, and 214 patients with CS from two centers were respectively enrolled into the training cohorts (institution 1, n = 113) and test cohorts (institution 2, n = 101). The intratumoral and peritumoral radiomics features were extracted from CT images. The intratumoral, peritumoral, and combined radiomics signatures were constructed respectively, and their radiomics scores (Rad-score) were calculated. The performance of intratumoral, peritumoral, and combined radiomics signatures in PFS prediction in patients with CS was evaluated by C-index, time-dependent area under the receiver operating characteristics curve (time-AUC), and time-dependent C-index (time C-index).

Results

Eleven, 7, and 16 features were used to construct the intratumoral, peritumoral, and combined radiomics signatures, respectively. The combined radiomics signature showed the best prediction ability in the training cohort (C-index, 0.835; 95%; confidence interval [CI], 0.764–0.905) and the test cohort (C-index, 0.800; 95% CI, 0.681–0.920). Time-AUC and time C-index showed that the combined signature outperformed the intratumoral and peritumoral radiomics signatures in the prediction of PFS.

Conclusion

The CT-based combined signature incorporating intratumoral and peritumoral radiomics features can predict PFS in patients with CS, which might assist clinicians in selecting individualized surveillance and treatment plans for CS patients.

Critical relevance statement

Develop and validate CT-based intratumoral, peritumoral, and combined radiomics signatures to evaluate the efficacy in predicting prognosis of patients with CS.

Key points

• Reliable prognostic models for preoperative chondrosarcoma are lacking.

• Combined radiomics signature incorporating intratumoral and peritumoral features can predict progression-free survival in patients with chondrosarcoma.

• Combined radiomics signature may facilitate individualized stratification and management of patients with chondrosarcoma.

Graphical Abstract
Performance of dual-layer spectrum CT virtual monoenergetic images to assess early rectal adenocarcinoma T-stage: comparison with MR
Authors: Jia Ziqi , Guo Lei , Yuan WenJing , Dai JianHao , Lu JianYe , Li ZhiQiang , Du Xiaohua , Chen Weicui , Liu Xian
Published: January 2024

Objectives

To evaluate the image quality and utility of virtual monoenergetic images (VMI) of dual-layer spectrum computed tomography (DLSCT) in assessing preoperative T-stage for early rectal adenocarcinoma (ERA).

Methods

This retrospective study included 67 ERA patients (mean age 62 ± 11.1 years) who underwent DLSCT and MR examination. VMI 40–200 keV and poly energetic image (PEI) were reconstructed. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and tumor contrast of different energy levels were calculated and compared, respectively. Two radiologists independently assess the image quality of the VMIs and PEI using 5-point scales. The diagnostic accuracies of DLSCT and HR-MRI for ERA T-staging were evaluated and compared.

Results

The maximum noise was observed at VMI 40 keV, and noise at VMI 40–200 keV in the arterial and venous phases showed no significant difference (all p > 0.05). The highest SNR and CNR were obtained at VMI 40 keV, significantly greater than other energy levels and PEI (all p < 0.05). Tumor contrast was more evident than PEI at 40–100 keV in the arterial phase and at 40 keV in the venous phase (all p < 0.05). When compared with PEI, VMI 40 keV yielded the highest scores for overall image quality, tumor visibility, and tumor margin delineation, especially in the venous phase (p < 0.05). The overall diagnostic accuracy of DLSCT and HR-MRI for T-stage was 65.67 and 71.64% and showed no significant difference (p > 0.05).

Conclusions

VMI 40 keV improves image quality and accuracy in identifying lesions, providing better diagnostic information for ERA staging.

Critical relevance statement

Low-keV VMI from DLSCT can improve tumor staging accuracy for early rectal carcinoma, helping guide surgical intervention decisions, and has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC.

Keypoints

• Compared with PEI, low-keV VIM derived from DLSCT, particularly at the 40 keV, significantly enhanced the objective and subjective image quality of ERA.

• Using VMI 40 keV helped increase lesion detectability, leading to improved diagnostic accuracy for ERA.

• Low-keV VMI from DLSCT has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC.

Graphical Abstract
A framework to integrate artificial intelligence training into radiology residency programs: preparing the future radiologist
Authors: van Kooten Maria Jorina , Tan Can Ozan , Hofmeijer Elfi Inez Saïda , van Ooijen Peter Martinus Adrianus , Noordzij Walter , Lamers Maria Jolanda , Kwee Thomas Christian , Vliegenthart Rozemarijn , Yakar Derya
Published: January 2024

Objectives

To present a framework to develop and implement a fast-track artificial intelligence (AI) curriculum into an existing radiology residency program, with the potential to prepare a new generation of AI conscious radiologists.

Methods

The AI-curriculum framework comprises five sequential steps: (1) forming a team of AI experts, (2) assessing the residents’ knowledge level and needs, (3) defining learning objectives, (4) matching these objectives with effective teaching strategies, and finally (5) implementing and evaluating the pilot. Following these steps, a multidisciplinary team of AI engineers, radiologists, and radiology residents designed a 3-day program, including didactic lectures, hands-on laboratory sessions, and group discussions with experts to enhance AI understanding. Pre- and post-curriculum surveys were conducted to assess participants’ expectations and progress and were analyzed using a Wilcoxon rank-sum test.

Results

There was 100% response rate to the pre- and post-curriculum survey (17 and 12 respondents, respectively). Participants’ confidence in their knowledge and understanding of AI in radiology significantly increased after completing the program (pre-curriculum means 3.25 ± 1.48 (SD), post-curriculum means 6.5 ± 0.90 (SD), p-value = 0.002). A total of 75% confirmed that the course addressed topics that were applicable to their work in radiology. Lectures on the fundamentals of AI and group discussions with experts were deemed most useful.

Conclusion

Designing an AI curriculum for radiology residents and implementing it into a radiology residency program is feasible using the framework presented. The 3-day AI curriculum effectively increased participants’ perception of knowledge and skills about AI in radiology and can serve as a starting point for further customization.

Critical relevance statement

The framework provides guidance for developing and implementing an AI curriculum in radiology residency programs, educating residents on the application of AI in radiology and ultimately contributing to future high-quality, safe, and effective patient care.

Key points

• AI education is necessary to prepare a new generation of AI-conscious radiologists.

• The AI curriculum increased participants’ perception of AI knowledge and skills in radiology.

• This five-step framework can assist integrating AI education into radiology residency programs.

Graphical Abstract
Translating radiological research into practice—from discovery to clinical impact
Authors: Smits Marion , Rockall Andrea , Constantinescu Stefan N. , Sardanelli Francesco , Martí-Bonmatí Luis
Published: January 2024

At the European Society of Radiology (ESR), we strive to provide evidence for radiological practices that improve patient outcomes and have a societal impact. Successful translation of radiological research into clinical practice requires multiple factors including tailored methodology, a multidisciplinary approach aiming beyond technical validation, and a focus on unmet clinical needs. Low levels of evidence are a threat to radiology, resulting in low visibility and credibility. Here, we provide the background and rationale for the thematic series Translating radiological research into practice—from discovery to clinical impact, inviting authors to describe their processes of achieving clinically impactful radiological research. We describe the challenges unique to radiological research. Additionally, a survey was sent to non-radiological clinical societies. The majority of respondents (6/11) were in the field of gastrointestinal/abdominal medicine. The implementation of CT/MRI techniques for disease characterisation, detection and staging of cancer, and treatment planning and radiological interventions were mentioned as the most important radiological developments in the past years. The perception was that patients are substantially unaware of the impact of these developments. Unmet clinical needs were mostly early diagnosis and staging of cancer, microstructural/functional assessment of tissues and organs, and implant assessment. All but one respondent considered radiology important for research in their discipline, but five indicated that radiology is currently not involved in their research. Radiology research holds the potential for being transformative to medical practice. It is our responsibility to take the lead in studies including radiology and strive towards the highest levels of evidence.

Critical relevance statement For radiological research to make a clinical and societal impact, radiologists should take the lead in radiological studies, go beyond the assessment of technical feasibility and diagnostic accuracy, and—in a multidisciplinary approach—address clinical unmet needs.

Key points

• Multiple factors are essential for radiological research to make a clinical and societal impact.

• Radiological research needs to go beyond diagnostic accuracy and address unmet clinical needs.

• Radiologists should take the lead in radiological studies with a multidisciplinary approach.

Graphical Abstract
MRI characteristics of chemotherapy-related central neurotoxicity: a pictorial review
Authors: Isaac Mina F. G. , Alkhatib Rugaiyah , Ho Chi Long
Published: January 2024

The relentless advancement of chemotherapeutic agents has enhanced survival rates among cancer patients. However, this success comes with an increased prevalence of chemotherapy-induced neurotoxicity, which often mimics the symptoms of metastatic disease or paraneoplastic syndromes and poses a diagnostic challenge for clinicians. Imaging, particularly MRI, plays a pivotal role in unraveling this conundrum.

This comprehensive review explores the MRI patterns associated with central neurotoxicities induced by various chemotherapeutic agents. Our objective is to provide radiologists and clinicians with illustrative diagrams that offer a structured approach to diagnosing these conditions. By enhancing the understanding of these distinctive MRI patterns, we aim to facilitate accurate and timely diagnosis, ultimately improving patient care in the context of evolving cancer treatments.

Critical relevance statement

This article describes the essential role of MRI in identifying distinct patterns of chemotherapy-induced central neurotoxicity, enabling early diagnosis and improved patient care within the field of clinical radiology.

Key points

• Chemotherapy-induced neurotoxicity is a growing concern for cancer patients, and MRI is a key tool in diagnosis.

• This review highlights distinctive MRI patterns associated with various chemotherapy-induced neurotoxicities.

• Understanding these patterns improves patient care, ensuring timely intervention and accurate diagnosis in the complex world of cancer treatment.

Graphical Abstract
Human intestinal organoid-derived PDGFRα + mesenchymal stroma enables proliferation and maintenance of LGR4 + epithelial stem cells
Authors: Chen JunLong , Horiuchi Shinichiro , Kuramochi So , Kawasaki Tomoyuki , Kawasumi Hayato , Akiyama Saeko , Arai Tomoki , Morinaga Kenichi , Kimura Tohru , Kiyono Tohru , Akutsu Hidenori , Ishida Seiichi , Umezawa Akihiro
Published: January 2024

Background

Intestinal epithelial cells derived from human pluripotent stem cells (hPSCs) are generally maintained and cultured as organoids in vitro because they do not exhibit adhesion when cultured. However, the three-dimensional structure of organoids makes their use in regenerative medicine and drug discovery difficult. Mesenchymal stromal cells are found near intestinal stem cells in vivo and provide trophic factors to regulate stem cell maintenance and proliferation, such as BMP inhibitors, WNT, and R-spondin. In this study, we aimed to use mesenchymal stromal cells isolated from hPSC-derived intestinal organoids to establish an in vitro culture system that enables stable proliferation and maintenance of hPSC-derived intestinal epithelial cells in adhesion culture.

Methods

We established an isolation protocol for intestinal epithelial cells and mesenchymal stromal cells from hPSCs-derived intestinal organoids and a co-culture system for these cells. We then evaluated the intestinal epithelial cells and mesenchymal stromal cells' morphology, proliferative capacity, chromosomal stability, tumorigenicity, and gene expression profiles. We also evaluated the usefulness of the cells for pharmacokinetic and toxicity studies.

Results

The proliferating intestinal epithelial cells exhibited a columnar form, microvilli and glycocalyx formation, cell polarity, and expression of drug-metabolizing enzymes and transporters. The intestinal epithelial cells also showed barrier function, transporter activity, and drug-metabolizing capacity. Notably, small intestinal epithelial stem cells cannot be cultured in adherent culture without mesenchymal stromal cells and cannot replaced by other feeder cells. Organoid-derived mesenchymal stromal cells resemble the trophocytes essential for maintaining small intestinal epithelial stem cells and play a crucial role in adherent culture.

Conclusions

The high proliferative expansion, productivity, and functionality of hPSC-derived intestinal epithelial cells may have potential applications in pharmacokinetic and toxicity studies and regenerative medicine.
SHC: soft-hard correspondences framework for simplifying point cloud registration
Authors: Chen Zhaoxiang , Yu Feng , Liu Shuqing , Cao Jiacheng , Xiao Zhuohan , Jiang Minghua
Published: January 2024

Point cloud registration is a multifaceted problem that involves a series of procedures. Many deep learning methods employ complex structured networks to achieve robust registration performance. However, these intricate structures can amplify the challenges of network learning and impede gradient propagation. To address this concern, the soft-hard correspondence (SHC) framework is introduced in the present paper to streamline the registration problem. The framework encompasses two modes: the hard correspondence mode, which transforms the registration problem into a correspondence pair search problem, and the soft correspondence mode, which addresses this new problem. The simplification of the problem provides two advantages. First, it eliminates the need for intermediate operations that lead to error fusion and counteraction, thereby improving gradient propagation. Second, a perfect solution is not necessary to solve the new problem, since accurate registration results can be achieved even in the presence of errors in the found pairs. The experimental results demonstrate that SHC successfully simplifies the registration problem. It achieves performance comparable to complex networks using a simple network and can achieve zero error on datasets with perfect correspondence pairs.
Risk of flare or relapse in patients with immune-mediated diseases following SARS-CoV-2 vaccination: a systematic review and meta-analysis
Authors: Shabani Mahya , Shobeiri Parnian , Nouri Shadi , Moradi Zahra , Amenu Robel Assefa , Mehrabi Nejad Mohammad-Mehdi , Rezaei Nima
Published: January 2024

Background

Patients with autoimmune and immune-mediated diseases (AI-IMD) are at greater risk of COVID-19 infection; therefore, they should be prioritized in vaccination programs. However, there are concerns regarding the safety of COVID-19 vaccines in terms of disease relapse, flare, or exacerbation. In this study, we aimed to provide a more precise and reliable vision using systematic review and meta-analysis.

Methods

PubMed-MEDLINE, Embase, and Web of Science were searched for original articles reporting the relapse/flare in adult patients with AI-IMD between June 1, 2020 and September 25, 2022. Subgroup analysis and sensitivity analysis were conducted to investigate the sources of heterogeneity. Statistical analysis was performed using R software.

Results

A total of 134 observations of various AI-IMDs across 74 studies assessed the rate of relapse, flare, or exacerbation in AI-IMD patients. Accordingly, the crude overall prevalence of relapse, flare, or exacerbation was 6.28% (95% CI [4.78%; 7.95%], I2 = 97.6%), changing from 6.28% (I2 = 97.6%) to 6.24% (I2 = 65.1%) after removing the outliers. AI-IMD patients administering mRNA, vector-based, and inactive vaccines showed 8.13% ([5.6%; 11.03%], I2 = 98.1%), 0.32% ([0.0%; 4.03%], I2 = 93.5%), and 3.07% ([1.09%; 5.9%], I2 = 96.2%) relapse, flare, or exacerbation, respectively (p-value = 0.0086). In terms of disease category, nephrologic (26.66%) and hematologic (14.12%) disorders had the highest and dermatologic (4.81%) and neurologic (2.62%) disorders exhibited to have the lowest crude prevalence of relapse, flare, or exacerbation (p-value < 0.0001).

Conclusion

The risk of flare/relapse/exacerbation in AI-IMD patients is found to be minimal, especially with vector-based vaccines. Vaccination against COVID-19 is recommended in this population.
Androgen deficiency is associated with a better prognosis in glioblastoma
Authors: Fariña-Jerónimo Helga , Martín-Ramírez Rita , González-Fernández Rebeca , Medina Lilian , de Vera Antonia , Martín-Vasallo Pablo , Plata-Bello Julio
Published: January 2024

Background

The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown.

Aim

This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma.

Methods

Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis.

Results

Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004).

Conclusion

Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.
The spatial patterning of emergency demand for police services: a scoping review
Authors: Langton Samuel , Ruiter Stijn , Schoonmade Linda
Published: January 2024

This preregistered scoping review provides an account of studies which have examined the spatial patterning of emergency reactive police demand (ERPD) as measured by calls for service data. To date, the field has generated a wealth of information about the geographic concentration of calls for service, but the information remains unsynthesised and inaccessible to researchers and practitioners. We code our literature sample (N = 79) according to the types of demand studied, the spatial scales used, the theories adopted, the methods deployed and the findings reported. We find that most studies focus on crime-related call types using meso-level (e.g., neighborhood) spatial scales. Descriptive methods demonstrate the non-random distribution of calls, irrespective of their type, while correlational findings are mixed, providing minimal support for theories such as social disorganization theory. We conclude with suggestions for future research, focusing on how the field can better exploit open data sources to ‘scale-up’ analyses.
Host genotype, soil composition, and geo-climatic factors shape the fonio seed microbiome
Authors: Tabassum Naheed , Ahmed Hanin Ibrahim , Parween Sabiha , Sheikh Arsheed H. , Saad Maged M. , Krattinger Simon G. , Hirt Heribert
Published: January 2024

Background

Fonio (Digitaria exilis), an orphan millet crop, is the oldest indigenous crop in West Africa. Although the yield is low due to pre-domestication characteristics, the quick maturation time, drought tolerance, and the ability to thrive on poor soils make fonio a climate-smart crop. Being holobionts, plants evolve in close interaction with microbial partners, which is crucial for plant phenology and fitness. As seeds are the bottleneck of vertically transmitting plant microbiota, we proposed to unravel the seed microbiome of the under-domesticated and resilient crop fonio. Our study investigated the bacterial seed endophyte diversity across 126 sequenced fonio accessions from distinct locations in West Africa. We conducted a correlation study of the structures and functions of the seed-associated microbiomes with the native geo-climate and soil structure data. We also performed Genome-wide association studies (GWAS) to identify genetic loci associated with seed endophyte diversity.

Result

We report that fonio millet has diverse heritable seed endophytic taxa. We analyzed the seed microbiomes of 126 fonio accessions and showed that despite the diversity of microbiomes from distinct geographical locations, all fonio genetic groups share a core microbiome. In addition, we observed that native soil composition, geo-climatic factors, and host genotype correlate with the seed microbiomes. GWAS analysis of genetic loci associated with endophyte seed bacterial diversity identified fonio SNPs associated with genes functioning in embryo development and stress/defense response.

Conclusion

Analysis of the seed endophyte of the climate-smart crop fonio indicated that despite possessing a heritable core microbiome, native conditions may shape the overall fonio seed microbiomes in different populations. These distinct microbiomes could play important roles in the adaptation of fonio to different environmental conditions. Our study identified the seed microbiome as a potential target for enhancing crop resilience to climate stress in a sustainable way.
BTLA biology in cancer: from bench discoveries to clinical potentials
Authors: Andrzejczak Anna , Karabon Lidia
Published: January 2024

Immune checkpoints play a critical role in maintaining the delicate balance of immune activation in order to prevent potential harm caused by excessive activation, autoimmunity, or tissue damage. B and T lymphocyte attenuator (BTLA) is one of crucial checkpoint, regulating stimulatory and inhibitory signals in immune responses. Its interaction with the herpes virus entry mediator (HVEM) plays an essential role in negatively regulating immune responses, thereby preserving immune homeostasis. In cancer, abnormal cells evade immune surveillance by exploiting checkpoints like BTLA. Upregulated BTLA expression is linked to impaired anti-tumor immunity and unfavorable disease outcomes. In preclinical studies, BTLA-targeted therapies have shown improved treatment outcomes and enhanced antitumor immunity. This review aims to provide an in-depth understanding of BTLA’s biology, its role in various cancers, and its potential as a prognostic factor. Additionally, it explores the latest research on BTLA blockade in cancer immunotherapy, offering hope for more effective cancer treatments.