bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach
Authors: Rujirachaivej Punchita , Siriboonpiputtana Teerapong , Choomee Kornkan , Supimon Kamonlapat , Sangsuwannukul Thanich , Songprakhon Pucharee , Natungnuy Krissada , Luangwattananun Piriya , Yuti Pornpimon , Junking Mutita , Yenchitsomanus Pa-thai 
Published: January 2025

Abstract

Background
Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.

Methods
To address these issues, we developed a lentiviral system to engineer T cells that secrete αB7-H3-αCD3 bispecific engager molecules (αB7-H3-αCD3 ENG-T cells). We evaluated their effectiveness against MM cells with varying B7-H3 expression levels, from B7-H3neg to B7-H3high.

Results
The αB7-H3-αCD3 ENG-T cells demonstrated significant anti-tumor activity against MM cell lines expressing B7-H3. SupT-1 cells (B7-H3neg) served as controls and exhibited minimal cytotoxicity from αB7-H3-αCD3 ENG T cells. In contrast, these engineered T cells showed dose-dependent killing of B7-H3-expressing MM cells: NCI-H929 (B7-H3low), L-363 (B7-H3medium), and KMS-12-PE (B7-H3high). For NCI-H929 cells, cytotoxicity reached 38.5 ± 7.4% (p = 0.0212) and 54.0 ± 9.2% (p = 0.0317) at effector-to-target (E:T) ratios of 5:1 and 10:1, respectively. Against L-363 cells, cytotoxicity was 56.6 ± 3.2% (p < 0.0001) and 71.4 ± 5.2% (p = 0.0002) at E:T ratios of 5:1 and 10:1, respectively. For KMS-12-PE cells, significant cytotoxic effects were observed even at an E:T ratio of 1:1, with 27.2 ± 3.7% (p = 0.0004), 44.4 ± 3.7% (p < 0.0001), and 68.6 ± 9.2% (p = 0.0004) cytotoxicity at E:T ratios of 1:1, 5:1, and 10:1, respectively.

Conclusions
These results indicate that αB7-H3-αCD3 ENG T cells could be a promising therapy for B7-H3-positive MM. They may enhance current MM treatments and improve overall outcomes. Additional preclinical and clinical research is required to fully assess their therapeutic potential.
Impacts of genomic alterations on the efficacy of HER2-targeted antibody–drug conjugates in patients with metastatic breast cancer
Authors: Huang Riqing , Hu Anqi , Rong Qixiang , Shu Ditian , Chen Meiting , Yang Wei , Zhang Yue , Zheng Qiufan , An Xin , Xue Cong , Li Haifeng , Shi Yanxia 
Published: January 2025

Abstract

Background
HER2-targeted antibody–drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.

Methods
This comprehensive real-world retrospective study collected clinical data from patients diagnosed with metastatic breast cancer and performed genomic profiling using targeted next-generation sequencing. The study analyzed the associations between genomic alterations and clinical outcomes of HER2 ADC treatment.

Results
Sixty-three patients were included in this study, 33 with HER2-low breast cancer and 30 with HER2-positive breast cancer, respectively. The most frequently altered genes were TP53 (69%), PIK3CA (45%), MYC (35%), and ERBB2 (35%). Patients with amplifications in cell cycle-related genes showed inferior median progression-free survival (PFS) than those without amplifications (2.07 months vs. 8.40 months; HR = 5.24; 95% CI 2.11–13.01; p < 0.001), particularly in HER2-low patients (2.07 months vs. 8.27 months; HR = 4.23; 95% CI 1.50–11.91; p = 0.004). Additionally, ERBB2/CDK12 co-amplification exhibited a superior median PFS in all patients (19.33 months vs. 5.43 months; HR = 0.13; 95% CI 0.04–0.45; p < 0.001) and in HER2-positive patients (19.33 months vs. 6.87 months; HR = 0.18; 95% CI 0.05–0.72; p = 0.007). Multivariate analysis indicated that amplification in cell cycle-related genes was an independent predictor of inferior PFS (HR = 4.46; 95% CI 1.08–18.40; p = 0.039), while the presence of ERBB2/CDK12 co-amplification was independently correlated with superior PFS (HR = 0.16; 95% CI 0.04–0.65; p = 0.010).

Conclusions
Amplification in cell cycle genes may contribute to primary resistance of HER2 ADC in HER2-low breast cancer. ERBB2/CDK12 co-amplification may be a potential biomarker for favorable responses in HER2-positive breast cancer.
Multi-disciplinary treatment of broncho-esophageal fistula in a high-risk single-lung patient
Authors: Haaverstad Rune , Ovrebo Kjell , Sandvik Lorentz , Seland Håvard , Husebø Gunnar Reksten , Ellensen Vegard Skalstad , Farstad Marit , Strandenes Eivind , Sharma Rajinder , Øksnes Marianne , Storesund Anders Kjellevold , Kolseth Solveig Moss 
Published: January 2025

Abstract
Background
A broncho-esophageal fistula (BEF) is a medical and surgical disaster. Treatment of BEF is often limited to palliative stent treatment that may migrate or cause erosions and tissue necrosis. Surgical repair of BEF is the only established definite treatment.

Case presentation
BEF presented in a 40-year-old female patient 8 years after curative treatment with pneumonectomy and radio-chemotherapy for advanced lung cancer. She had autoimmune comorbidity, a single lung, vocal cord paralysis and an extremely hostile thorax. Multi-disciplinary collaboration, close patient involvement and evaluation by the hospital medical ethics committee were key elements in the following treatment course. After temporary stent treatment, a carefully staged surgical marathon was performed: Veno-venous ECMO was established to secure oxygenation, and bilateral thoracotomy and laparotomy performed to access structures in the frozen mediastinum. After extensive thoracoplasty and high-risk dissection, esophagectomy was performed and the 20 × 35 mm bronchial defect repaired by bronchoplasty with a latissimus muscle flap. It was complicated by thrombotic occlusion of the upper venous system, repeated postoperative bleedings and critical illness neuropathy. The patient recovered and was discharged 150 days after surgery. Within 1–2 years bronchoscopy showed a smooth undiscernible bronchoplasty with a stable open left main bronchus. At 5 years the patient lives an independent life at home with her family.

Conclusions
Surgical treatment of BEF in an extremely complex patient may turn out successfully. It demands careful ethical considerations, comprehensive surgical strategy, multi-disciplinary teamwork, and shared decision making with the patient. The patient presented in this case report is closely followed up with good life quality after 5 years.
Specific plasma metabolite profile in intestinal Behçet’s syndrome
Authors: Hou Cheng-cheng , Bao Hua-fang , She Chun-hui , Chen Hua-yu , Pan Guan-xing , Chen Hua-ning , Rui Hong-bing 
Published: January 2025

Abstract

Background
Intestinal Behçet’s syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.

Methods
In this study, we performed a global untargeted metabolomics approach in plasma samples from 30 IBS patients and 20 healthy subjects. P value < 0.05 and variable importance projection (VIP) values > 1 were considered to be statistically significant metabolites. Univariate receiver operating characteristic (ROC) curve analysis was plotted as a measure for assessing the clinical performance of metabolites, and area under curve (AUC) were assessed.

Results
A total of 147 differentially abundant metabolites (DAMs) were identified between IBS patients and normal control (NC) group. The potential pathways involved in the pathogenesis of IBS include linoleic acid metabolism; GABAergic synapse; biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; ovarian steroidogenesis; and others. In addition, a total of 103 significant metabolites were selected to distinguish active IBS from inactive IBS patients. Tyrosine metabolism, dopaminergic synapse and neuroactive ligand-receptor interaction were found to be closely related to the disease activity of IBS. Furthermore, three potential metabolites including quinate, stearidonic acid (SDA) and capric acid (CA) could significantly differ IBS patients from NC group. On the other hand, 1-methyladenosine (m1A), genipin, methylmalonic acid (MMA) and ascorbate could significantly differentiated active IBS from inactive IBS patients.

Conclusion
In conclusion, this study demonstrated the characteristic plasma metabolic profiles between IBS group and NC group, as well as between active and inactive IBS patients by using an untargeted LC/MS metabolomics profiling approach. In this study, quinate, SDA and CA were identified as potential diagnostic biomarkers for IBS. Additionally, m1A, genipin, MMA and ascorbate could serve as potential biomarkers for evaluating IBS activity. These findings might provide potential valuable insights for developing therapeutic strategies to manage IBS in the future.
Unraveling the genetic spectrum of inherited deaf-blindness in Portugal
Authors: Machado Telma , Cortinhal Telmo , Carvalho Ana Luísa , Teixeira-Marques Francisco , Silva Rufino , Murta Joaquim , Marques João Pedro 
Published: January 2025

Abstract

Background
Syndromic genetic disorders affecting vision can also cause hearing loss, and Usher syndrome is by far the most common etiology. However, many other conditions can present dual sensory impairment. Accurate diagnosis is essential for providing patients with genetic counseling, prognostic information, and appropriate resources. This study aimed to describe the genetic profile of combined inherited deaf-blindness in Portugal.

Methods
This was a cross-sectional study conducted at a tertiary hospital in Portugal. Patients were identified through the national, web-based inherited retinal dystrophies registry (IRD-PT, retina.com.pt). Demographics, clinical, and genetic data were retrieved from individual patient records. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for solved cases.

Results
Eighty-four patients (58.3% males; mean age 40.0 ± 17.9 years) from 71 families were included. Usher syndrome was the most frequent etiology (71.4%) followed by Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract syndrome (6.0%), Autosomal dominant optic atrophy plus (4.8%) and cone-rod dystrophy and hearing loss (4.8%). Other less frequent etiologies included Alport syndrome (2.4%), Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (2.4%), Heimler syndrome (2.4%), Senior-Loken syndrome (1.2%), Waardenburg syndrome (1.2%), Maternally inherited diabetes and deafness (1.2%), and Stickler syndrome (1.2%). The overall diagnostic yield of deleterious variants in our deaf–blind cohort was 73.2%. A total of 55 genetic variants were identified across 16 different genes; 11 of these variants are novel and herein reported for the first time.

Conclusions
This is the first study to describe the genetic profile of patients with dual sensory impairment in Portugal, highlighting the genetic heterogeneity associated with inherited deaf-blindness. Usher syndrome was the most prevalent cause in this cohort. Nevertheless, several other less frequent causes must also be considered. This study showed a high diagnostic yield and reported 11 novel genetic variants, thereby contributing to expand the mutational spectrum of these conditions.
RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington’s disease models
Authors: Lin Yingqi , Li Caijuan , Chen Yizhi , Gao Jiale , Li Jiawei , Huang Chunhui , Liu Zhaoming , Wang Wei , Zheng Xiao , Song Xichen , Wu Jianhao , Wu Jiaxi , Luo Oscar Junhong , Tu Zhuchi , Li Shihua , Li Xiao-Jiang , Lai Liangxue , Yan Sen 
Published: January 2025

Abstract

Background
HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention.

Methods
The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA. This therapeutic effect was substantiated in various models: HEK 293 T cell, the HD 140Q-KI mouse, and the HD-KI pig model. The efficiency of the knockdown was analyzed through Western blot and RT-qPCR. Additionally, neuropathological changes were examined using Western blot, immunostaining, and RNA sequencing. The impact on motor abilities was assessed via behavioral experiments, providing a comprehensive evaluation of the treatment's effectiveness.

Results
CRISPR/CasRx system can significantly reduce HTT mRNA levels across various models, including HEK 293 T cells, HD 140Q-KI mice at various disease stages, and HD-KI pigs, and resulted in decreased expression of mHTT. Utilizing the CRISPR/CasRx system to knock down HTT RNA has shown to ameliorate gliosis in HD 140Q-KI mice and delay neurodegeneration in HD pigs.

Conclusions
These findings highlight the effectiveness of the RNA-targeting CRISPR/CasRx as a potential therapeutic strategy for HD. Furthermore, the success of this approach provides valuable insights and novel avenues for the treatment of other genetic disorders caused by gene mutations.
Automatic segmentation model and machine learning model grounded in ultrasound radiomics for distinguishing between low malignant risk and intermediate-high malignant risk of adnexal masses
Authors: Liu Lu , Cai Wenjun , Zheng Feibo , Tian Hongyan , Li Yanping , Wang Ting , Chen Xiaonan , Zhu Wenjing 
Published: January 2025

Abstract

Objective
To develop an automatic segmentation model to delineate the adnexal masses and construct a machine learning model to differentiate between low malignant risk and intermediate-high malignant risk of adnexal masses based on ovarian-adnexal reporting and data system (O-RADS).

Methods
A total of 663 ultrasound images of adnexal mass were collected and divided into two sets according to experienced radiologists: a low malignant risk set (n = 446) and an intermediate-high malignant risk set (n = 217). Deep learning segmentation models were trained and selected to automatically segment adnexal masses. Radiomics features were extracted utilizing a feature analysis system in Pyradiomics. Feature selection was conducted using the Spearman correlation analysis, Mann–Whitney U-test, and least absolute shrinkage and selection operator (LASSO) regression. A nomogram integrating radiomic and clinical features using a machine learning model was established and evaluated. The SHapley Additive exPlanations were used for model interpretability and visualization.

Results
The FCN ResNet101 demonstrated the highest segmentation performance for adnexal masses (Dice similarity coefficient: 89.1%). Support vector machine achieved the best AUC (0.961, 95% CI: 0.925–0.996). The nomogram using the LightGBM algorithm reached the best AUC (0.966, 95% CI: 0.927–1.000). The diagnostic performance of the nomogram was comparable to that of experienced radiologists (p > 0.05) and outperformed that of less-experienced radiologists (p < 0.05). The model significantly improved the diagnostic accuracy of less-experienced radiologists.

Conclusions
The segmentation model serves as a valuable tool for the automated delineation of adnexal lesions. The machine learning model exhibited commendable classification capability and outperformed the diagnostic performance of less-experienced radiologists.

Critical relevance statement
The ultrasound radiomics-based machine learning model holds the potential to elevate the professional ability of less-experienced radiologists and can be used to assist in the clinical screening of ovarian cancer.

Key Points

We developed an image segmentation model to automatically delineate adnexal masses.

We developed a model to classify adnexal masses based on O-RADS.

The machine learning model has achieved commendable classification performance.

The machine learning model possesses the capability to enhance the proficiency of less-experienced radiologists.

We used SHapley Additive exPlanations to interpret and visualize the model.

Graphical Abstract
Decoding the future: a bibliometric exploration of blockchain in logistics
Authors: Fernández Moreno Mª Del Valle , Alcántara-Pilar Juan Miguel , Tolentino Marta 
Published: January 2025

Abstract
This paper presents the results of a bibliometric analysis concerning the application of blockchain technology to logistics. It aims to discern the relational structure among past and current topics, predict emerging trends, and provide a longitudinal perspective on this research domain. Using co-word analysis techniques, we employ SciMAT software to analyze over 800 papers from 2016 to March 2023. The investigation enhances the understanding of blockchain technology, revealing that scientific production in this area revolves around eight primary thematic clusters. Visual representations of the results are provided through longitudinal maps and strategic diagrams, illustrating pivotal themes across the three study periods: blockchain and sustainability. Smart contracts emerge as a focal topic in the final period under consideration.
Civil society organisations and the local politics of migration: how funding contexts matter
Authors: Lang Christine , Badenhoop Elisabeth 
Published: January 2025

Abstract
Migration studies have highlighted the crucial role of civil society organisations (CSOs) in the local politics of migration. Less explored is the impact of the material conditions under which CSOs operate. And yet CSOs delivering public services to migrant and racialised populations often rely on public funding which has been significantly restructured since neoliberal welfare reforms in many Western countries in the 1990s. This article examines how funding contexts shape the opportunities of CSOs to influence local policymaking on migration and migration-related change from a cross-country and cross-city comparative perspective. Based on the empirical analysis of four cities in France and Germany and a comprehensive dataset comprising interviews, observations and documents, we argue that funding contexts significantly impact on CSOs’ potential to shape local policymaking. They do so by enhancing and restricting (1) CSOs’ access to spaces of policymaking as well as (2) CSOs’ capacities for political engagement. We demonstrate the mediating importance of specific funding structures and politics at both national and local scales as well as the role of state-CSO relations in manifesting and reproducing these funding contexts.
‘This settlement is just a launch pad to move to better city spaces’: radical sense of place and migration aspirations among youth migrants in the diaspora
Authors: Bhanye Johannes , Matamanda Abraham , Shayamunda Ruvimbo 
Published: January 2025

Abstract
This ethnographic study investigates the perceptions of place and migration aspirations among young migrants within the Malawian diaspora in Lydiate, an informal settlement in Zimbabwe. Unlike traditional conceptions of diaspora that emphasize long-term settlement and place attachment, this study introduces the concept of a ‘radical sense of place,’ where the settlement is viewed not as a permanent home but as a temporary staging ground for future aspirations. Through qualitative data collected between 2018 and 2020, including participant observations and in-depth interviews with young migrants aged 15 to 35, this research explores how these youths strategically navigate their socio-economic marginalization. The findings reveal that young migrants perceive their settlement as a launch pad to better opportunities in more affluent urban areas, driven by a combination of harsh living conditions and the allure of urban life. This perspective challenges existing migration theories by highlighting the temporary and strategic relationships with place among diaspora youths. The study also highlights the interplay between age, identity, and aspirations, showcasing the pivotal role these factors play in shaping the radical decisions of young migrants. While young migrants exhibit resilience in the migration process, they also face social exclusion, lack of social protection, and the risk of abuse and discrimination. The study advocates for policies tailored to address the specific conditions and vulnerabilities faced by youths in diaspora ethnic enclaves, promoting avenues for meaningful employment and advocating for youth migration based on informed choices rather than forced migration.
Evaluation of a content-based image retrieval system for radiologists in high-resolution CT of interstitial lung diseases
Authors: Böttcher Benjamin , van Assen Marly , Fari Roberto , von Knebel Doeberitz Philipp L. , Kim Eun Young , Berkowitz Eugene A. , Meinel Felix G. , De Cecco Carlo N. 
Published: January 2025

Abstract

Background
This retrospective study aims to evaluate the impact of a content-based image retrieval (CBIR) application on diagnostic accuracy and confidence in interstitial lung disease (ILD) assessment using high-resolution computed tomography CT (HRCT).

Methods
Twenty-eight patients with verified pattern-based ILD diagnoses were split into two equal datasets (1 and 2). The images were assessed by two radiology residents (3rd and 5th year) and one expert radiologist in four sessions. Dataset 1 was used for sessions A and C, assessing diagnostic accuracy and confidence with mandatory and without CBIR software. Dataset 2 was used for sessions B and D with optional CBIR use, assessing time spending and frequency of CBIR usage. Accuracy was assessed on the CT pattern level, comparing readers’ diagnoses with reference diagnoses and CBIR results with region-of-interest (ROI) patterns.

Results
Diagnostic accuracy and confidence of readers showed an increasing trend with CBIR use compared to no CBIR use (53.6% versus 35.7% and 50.0% versus 32.2%, respectively). Time for reading significantly decreased in both datasets (A versus C: 104 s versus 54 s, p < 0.001; B versus D: 88.5 s versus 70 s, p = 0.009), whereas time for research increased with CBIR software use (A versus C: 31 s versus 81 s, p = 0.040). CBIR results showed a high pattern-based accuracy of overall 73.4%. Comparison between readers indicates a slightly higher accuracy of CBIR results when more than one ROI was used as input (77.7% versus 70.1%).

Conclusion
CBIR software improves in-training radiologist diagnostic accuracy and confidence while reducing interpretation time in ILD assessment.

Relevance statement
Content-based image retrieval software improves the assessment of interstitial lung diseases (ILD) in high-resolution CT, especially for radiology residents, by increasing diagnostic accuracy and confidence while reducing interpretation time. This can provide educational benefits and more time-efficient management of complex cases.

Key Points

A content-based image retrieval (CBIR) software improves diagnostic accuracy and confidence for in-training radiologists for interstitial lung disease (ILD) assessment on computed tomography (CT).

A CBIR application provides condensed information about similar HRCT cases reducing time for ILD assessment.

CBIR algorithms benefit from the input of multiple regions of interest per ILD case.

Graphical Abstract