bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of cervical spinal stenosis by automated 3D MRI segmentation of spinal cord and cerebrospinal fluid space
Authors: Hohenhaus Marc , Klingler Jan-Helge , Scholz Christoph , Watzlawick Ralf , Hubbe Ulrich , Beck Jürgen , Reisert Marco , Würtemberger Urs , Kremers Nico , Wolf Katharina 
Published: April 2024

Abstract
Design
Prospective diagnostic study.

Objectives
Anatomical evaluation and graduation of the severity of spinal stenosis is essential in degenerative cervical spine disease. In clinical practice, this is subjectively categorized on cervical MRI lacking an objective and reliable classification. We implemented a fully-automated quantification of spinal canal compromise through 3D T2-weighted MRI segmentation.

Setting
Medical Center - University of Freiburg, Germany.

Methods
Evaluation of 202 participants receiving 3D T2-weighted MRI of the cervical spine. Segments C2/3 to C6/7 were analyzed for spinal cord and cerebrospinal fluid space volume through a fully-automated segmentation based on a trained deep convolutional neural network. Spinal canal narrowing was characterized by relative values, across sever segments as adapted Maximal Canal Compromise (aMCC), and within the index segment as adapted Spinal Cord Occupation Ratio (aSCOR). Additionally, all segments were subjectively categorized by three observers as “no”, “relative” or “absolute” stenosis. Computed scores were applied on the subjective categorization.

Results
798 (79.0%) segments were subjectively categorized as “no” stenosis, 85 (8.4%) as “relative” stenosis, and 127 (12.6%) as “absolute” stenosis. The calculated scores revealed significant differences between each category (p ≤ 0.001). Youden’s Index analysis of ROC curves revealed optimal cut-offs to distinguish between “no” and “relative” stenosis for aMCC = 1.18 and aSCOR = 36.9%, and between “relative” and “absolute” stenosis for aMCC = 1.54 and aSCOR = 49.3%.

Conclusion
The presented fully-automated segmentation algorithm provides high diagnostic accuracy and objective classification of cervical spinal stenosis. The calculated cut-offs can be used for convenient radiological quantification of the severity of spinal canal compromise in clinical routine.
The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer
Authors: Pai Chun-Peng , Wang Han , Seachrist Darcie D. , Agarwal Neel , Adams Joshua A. , Liu Zhenghao , Keri Ruth A. , Cao Kaixiang , Schiemann William P. , Kao Hung-Ying 
Published: April 2024

AbstractThe alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model. Moreover, PML1, rather than the well-known tumor suppressor isoform PML4, rescues the proliferation of PML knockdown cells. ChIP-seq analysis reveals significant overlap between PML-, ER-, and Myc-bound promoters, suggesting their coordinated regulation of target gene expression, including genes involved in breast cancer stem cells (BCSCs), such as JAG1, KLF4, YAP1, SNAI1, and MYC. Loss of PML reduces BCSC-related gene expression, and exogenous PML1 expression elevates their expression. Consistently, PML1 restores the association of PML with these promoters in PML-depleted cells. We identified a novel association between PML1 and WDR5, a key component of H3K4 methyltransferase (HMTs) complexes that catalyze H3K4me1 and H3K4me3. ChIP-seq analyses showed that the loss of PML1 reduces H3K4me3 in numerous loci, including BCSC-associated gene promoters. Additionally, PML1, not PML4, re-establishes the H3K4me3 mark on these promoters in PML-depleted cells. Significantly, PML1 is essential for recruiting WDR5, MLL1, and MLL2 to these gene promoters. Inactivating WDR5 by knockdown or inhibitors phenocopies the effects of PML1 loss, reducing BCSC-related gene expression and tumorsphere formation and enhancing fulvestrant’s anticancer activity. Our findings challenge the conventional understanding of PML as a tumor suppressor, redefine its role as a promoter of tumor growth in breast cancer, and offer new insights into the unique roles of PML isoforms in breast cancer.
Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning
Authors: Tian Fei , Liu Dong , Wei Na , Fu Qianqian , Sun Lin , Liu Wei , Sui Xiaolong , Tian Kathryn , Nemeth Genevieve , Feng Jingyu , Xu Jingjing , Xiao Lin , Han Junya , Fu Jingjie , Shi Yinhua , Yang Yichen , Liu Jia , Hu Chunhong , Feng Bin , Sun Yan , Wang Yunjun , Yu Guohua , Kong Dalu , Wang Meiyun , Li Wencai , Chen Kexin , Li Xiangchun 
Published: April 2024

AbstractCancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists’ diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.
Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes
Authors: Hivert Marie-France , White Frédérique , Allard Catherine , James Kaitlyn , Majid Sana , Aguet François , Ardlie Kristin G. , Florez Jose C. , Edlow Andrea G. , Bouchard Luigi , Jacques Pierre-Étienne , Karumanchi S. Ananth , Powe Camille E. 
Published: April 2024

AbstractReduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source. Higher circulating IGFBP1 levels were associated with greater insulin sensitivity (lesser insulin resistance) at ~26 weeks gestation in the same cohort and in two additional pregnancy cohorts. In addition, low circulating IGFBP1 levels in early pregnancy predicted subsequent GDM diagnosis in two cohorts of pregnant women. These results implicate IGFBP1 in the glycemic physiology of pregnancy and suggest a role for placental IGFBP1 deficiency in GDM pathogenesis.
Phenomics and transcriptomic profiling of fruit development in distinct apple varieties
Authors: Zhang Weihan , Han Yuepeng , Liao Liao 
Published: April 2024

AbstractApple is one of the most economically important and popular temperate fruit trees. The domestication of apple has resulted in substantial phenotypic differences, particularly between wild and cultivated varieties. However, the relationship between gene expression and phenotypic variations in apple remains poorly understood. Here, we present a comprehensive dataset featuring five distinct apple varieties, including two wild varieties and three representative cultivated varieties. The dataset comprises of both phenomics data, encompassing twelve fruit quality-related traits continuously measured over two years, and transcriptomic data obtained at different developmental stages with three biological replicates. We performed basic quality control process, gene expression normalization and differential gene expression analysis to demonstrate the utility and reliability of the dataset. Our findings indicate that gene expression strongly related with phenotypic variations in apple. This dataset serves as a valuable resource, encompassing phenomics and transcriptomic data in multiple formats, thereby facilitating further exploration of the relationships between gene expression and phenotypic traits in apple.
Analyzing to discover origins of CNNs and ViT architectures in medical images
Authors: Oh Seungmin , Kim Namkug , Ryu Jongbin 
Published: April 2024

AbstractIn this paper, we introduce in-depth the analysis of CNNs and ViT architectures in medical images, with the goal of providing insights into subsequent research direction. In particular, the origins of deep neural networks should be explainable for medical images, but there has been a paucity of studies on such explainability in the aspect of deep neural network architectures. Therefore, we investigate the origin of model performance, which is the clue to explaining deep neural networks, focusing on the two most relevant architectures, such as CNNs and ViT. We give four analyses, including (1) robustness in a noisy environment, (2) consistency in translation invariance property, (3) visual recognition with obstructed images, and (4) acquired features from shape or texture so that we compare origins of CNNs and ViT that cause the differences of visual recognition performance. Furthermore, the discrepancies between medical and generic images are explored regarding such analyses. We discover that medical images, unlike generic ones, exhibit class-sensitive. Finally, we propose a straightforward ensemble method based on our analyses, demonstrating that our findings can help build follow-up studies. Our analysis code will be publicly available.
Urban greening with shrubs can supercharge invertebrate abundance and diversity
Authors: Sharmin Mahmuda , Tjoelker Mark G. , Esperon-Rodriguez Manuel , Katlav Alihan , Gilpin Amy-Marie , Rymer Paul D. , Power Sally A. 
Published: April 2024

AbstractIn urban areas, diverse and complex habitats for biodiversity are often lacking. This lack of diversity not only compromises essential ecological processes, such as pollination and nutrient cycling, but also diminishes the resilience of urban ecosystems to pests and diseases. To enhance urban biodiversity, a possible solution is to integrate shrubs alongside trees, thereby increasing the overall amount of vegetation, structural complexity and the associated resource diversity. Here, using a common garden experiment involving a variety of trees and shrubs planted alone and in combination, we evaluate how canopy-associated invertebrate assemblages are influenced by vegetation type. In particular, we test whether the presence of shrubs, alone or with trees, results in increased abundance and taxonomic richness of invertebrates, compared to trees on their own. We found that the overall abundance of invertebrates, and that of specific functional groups (e.g., herbivores, pollinators, detritivores), was higher on shrubs, compared to trees, and when trees and shrubs were planted in combination (relative to trees on their own). Our results suggest that planting shrub and tree species with wide and dense crowns can increase the associated abundance and taxonomic and functional group richness of invertebrate communities. Overall, our findings indicate that urban planning would benefit from incorporating shrubs alongside urban trees to maximise invertebrate abundance, diversity and function in urban landscapes.
Barriers to the use of tests for early detection of colorectal cancer in Chile
Authors: Alfaro Gabriela , Berger Zoltan , Mondschein Susana , Subiabre Felipe , Yankovic Natalia 
Published: April 2024

AbstractThis study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.
Label-free separation of peripheral blood mononuclear cells from whole blood by gradient acoustic focusing
Authors: Alsved Julia , Rezayati Charan Mahdi , Ohlsson Pelle , Urbansky Anke , Augustsson Per 
Published: April 2024

AbstractEfficient techniques for separating target cells from undiluted blood are necessary for various diagnostic and research applications. This paper presents acoustic focusing in dense media containing iodixanol to purify peripheral blood mononuclear cells (PBMCs) from whole blood in a label-free and flow-through format. If the blood is laminated or mixed with iodixanol solutions while passing through the resonant microchannel, all the components (fluids and cells) rearrange according to their acoustic impedances. Red blood cells (RBCs) have higher effective acoustic impedance than PBMCs. Therefore, they relocate to the pressure node despite the dense medium, while PBMCs stay near the channel walls due to their negative contrast factor relative to their surrounding medium. By modifying the medium and thus tuning the contrast factor of the cells, we enriched PBMCs relative to RBCs by a factor of 3600 to 11,000 and with a separation efficiency of 85%. That level of RBC depletion is higher than most other microfluidic methods and similar to that of density gradient centrifugation. The current acoustophoretic chip runs up to 20 µl/min undiluted whole blood and can be integrated with downstream analysis.
Automated quantification of avian influenza virus antigen in different organs
Authors: Landmann Maria , Scheibner David , Gischke Marcel , Abdelwhab Elsayed M. , Ulrich Reiner 
Published: April 2024

AbstractAs immunohistochemistry is valuable for determining tissue and cell tropism of avian influenza viruses (AIV), but time-consuming, an artificial intelligence-based workflow was developed to automate the AIV antigen quantification. Organ samples from experimental AIV infections including brain, heart, lung and spleen on one slide, and liver and kidney on another slide were stained for influenza A-matrixprotein and analyzed with QuPath: Random trees algorithms were trained to identify the organs on each slide, followed by threshold-based quantification of the immunoreactive area. The algorithms were trained and tested on two different slide sets, then retrained on both and validated on a third set. Except for the kidney, the best algorithms for organ selection correctly identified the largest proportion of the organ area. For most organs, the immunoreactive area assessed following organ selection was significantly and positively correlated to a manually assessed semiquantitative score. In the validation set, intravenously infected chickens showed a generally higher percentage of immunoreactive area than chickens infected oculonasally. Variability between the slide sets and a similar tissue texture of some organs limited the ability of the algorithms to select certain organs. Generally, suitable correlations of the immunoreactivity data results were achieved, facilitating high-throughput analysis of AIV tissue tropism.
Exploiting high-quality reconstruction image encryption strategy by optimized orthogonal compressive sensing
Authors: Wen Heping , Yang Lincheng , Bai Chixin , Lin Yiting , Liu Tengyu , Chen Lei , Hu Yingchun , He Daojing 
Published: April 2024

AbstractCompressive sensing is favored because it breaks through the constraints of Nyquist sampling law in signal reconstruction. However, the security defects of joint compression encryption and the problem of low quality of reconstructed image restoration need to be solved urgently. In view of this, this paper proposes a compressive sensing image encryption scheme based on optimized orthogonal measurement matrix. Utilizing a combination of DWT and OMP, along with chaos, the proposed scheme achieves high-security image encryption and superior quality in decryption reconstruction. Firstly, the orthogonal optimization method is used to improve the chaotic measurement matrix. Combined with Part Hadamard matrix, the measurement matrix with strong orthogonal characteristics is constructed by Kronecker product. Secondly, the original image is sparsely represented by DWT. Meanwhile, Arnold scrambling is used to disturb the correlation between its adjacent pixels. Following this, the image is compressed and measured in accordance with the principles of compressive sensing and obtain the intermediate image to be encrypted. Finally, the chaotic sequence generated based on 2D-LSCM is used to perform on odd-even interleaved diffusion and row-column permutation at bit-level to obtain the final ciphertext. The experimental results show that this scheme meets the cryptographic requirements of obfuscation, diffusion and avalanche effects, and also has a large key space, which is sufficient to resist brute-force cracking attacks. Based on the sparse and reconstruction algorithm of compressive sensing proposed in this paper, it has better image restoration quality than similar algorithms. Consequently, the compressive sensing image encryption scheme enhances both security and reconstruction quality, presenting promising applications in the evolving landscape of privacy protection for network big data.
Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues
Authors: Oishi Mayumi , Shinjo Keiko , Takanari Keisuke , Muraoka Ayako , Suzuki Miho M. , Kanbe Miki , Higuchi Shinichi , Ebisawa Katsumi , Hashikawa Kazunobu , Kamei Yuzuru , Kondo Yutaka 
Published: April 2024

AbstractKeloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.
Comparative evaluation of ten blood biomarkers of inflammation in regular heated tobacco users and non-smoking healthy males–a pilot study
Authors: Świątkowska Beata , Jankowski Mateusz , Kaleta Dorota 
Published: April 2024

AbstractHeated tobacco products (HTPs) are novel tobacco products that are alternatives to cigarettes. The study aimed to investigate the effect of HTPs on blood biomarkers of inflammation as well as to provide a comparative evaluation between daily heated tobacco users and healthy men who do not use nicotine products. This case–control study was carried out among 92 healthy males in Poland (Lodz-Province) aged 20–56 years: 44 daily heated tobacco users (daily use in the past 90 days) and 48 controls who do not use nicotine products. The history of use of the nicotine-containing products was self-reported and verified using a saliva cotinine test. A 20 ml blood sample was collected and the levels of ten blood biomarkers were analyzed. Among all heated tobacco users (n = 44), only the levels of interleukin 8 (IL-8) were significantly higher when compared to controls: 6.86 vs. 3.95 (p = 0.01). Among exclusive heated tobacco users (n = 33), the levels of IL-8 were also significantly higher when compared to controls: 7.76 vs. 3.95 (p = 0.01). IL-8 level was positively correlated (r = 0.37; p = 0.01) with the daily number of heated tobacco sticks. Out of 10 different biomarkers of inflammation, only IL-8 levels were significantly elevated in heated tobacco use compared to controls.
Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats
Authors: Amirkhosravi Arian , Mirtajaddini Goki Maryamossadat , Heidari Mahmoud Reza , Karami-Mohajeri Somayyeh , Iranpour Maryam , Torshabi Maryam , Mehrabani Mitra , Mandegary Ali , Mehrabani Mehrnaz 
Published: April 2024

AbstractPirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.