bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive Parallel Sorting of Particles Using Unwound Polygonal Vortex Beams
Authors: Li Xiaofei , Zhang Hao , Gao Yuanmei , Gbur Greg , Cai Yangjian , Yuan Yangsheng
Published: March 2022

Optical sorting, as one kind of optical tweezers, is used to separate mixed particles in a background environment. This unusual tool has a wide application prospect because the non-contact and non-destructive advantages ideally suit the pressing need of bio-technology. However, most sorting methods and devices have been accomplished based on real-time one-by-one sorting, which ignored the sorting efficiency and is not applicable to high-capacity particles. Although more and more structured light beams are proposed to enhance the sorting efficiency, it is still not enough for desired applications. Here, we propose a method for the massive parallel sorting of particles: polygonal optical vortex (OV) beams are unwound by a geometric transformation to produce linear OV beams with kinked distributions. This structured light is used to greatly enhance the sorting efficiency. We adopt the fractal theory to illustrate the increase of the region over which the beam can interact with particles. We demonstrate that the gradient force of this beam is large enough to manipulate spherical particles in the Rayleigh regime of scattering. These results introduce new possibilities for high-capacity particle sorting.
Oxidative RNA Damage in the Pathogenesis and Treatment of Type 2 Diabetes
Authors: Chen Xiatian , Yu Hua , Li Zhe , Ye Wei , Liu Ziqian , Gao Jinning , Wang Yin , Li Xin , Zhang Lei , Alenina Natalia , Bader Michael , Ding Hongyan , Li Peifeng , Aung Lynn Htet Htet
Published: March 2022

Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.
Role of the Air-Blood Barrier Phenotype in Lung Oxygen Uptake and Control of Extravascular Water
Authors: Miserocchi Giuseppe , Beretta Egidio , Rivolta Ilaria , Bartesaghi Manuela
Published: March 2022

The air blood barrier phenotype can be reasonably described by the ratio of lung capillary blood volume to the diffusion capacity of the alveolar membrane (Vc/Dm), which can be determined at rest in normoxia. The distribution of the Vc/Dm ratio in the population is normal; Vc/Dm shifts from ∼1, reflecting a higher number of alveoli of smaller radius, providing a high alveolar surface and a limited extension of the capillary network, to just opposite features on increasing Vc/Dm up to ∼6. We studied the kinetics of alveolar-capillary equilibration on exposure to edemagenic conditions (work at ∼60% maximum aerobic power) in hypoxia (HA) (PIO2 90 mmHg), based on an estimate of time constant of equilibration (τ) and blood capillary transit time (Tt). A shunt-like effect was described for subjects having a high Vc/Dm ratio, reflecting a longer τ (>0.5 s) and a shorter Tt (<0.8 s) due to pulmonary vasoconstriction and a larger increase in cardiac output (>3-fold). The tendency to develop lung edema in edemagenic conditions (work in HA) was found to be directly proportional to the value of Vc/Dm as suggested by an estimate of the mechanical properties of the respiratory system with the forced frequency oscillation technique.
Antioxidant, Transcriptome and the Metabolome Response to Dietary Astaxanthin in Exopalaemon carinicauda
Authors: Li Wenyang , Wang Jiajia , Li Jitao , Liu Ping , Li Jian , Zhao Fazhen
Published: March 2022

Astaxanthin (Axn), a feed additive, is becoming increasingly important for modulating the metabolism, growth, development, and reproduction of aquatic organisms in aquaculture. In this study, Exopalaemon carinicauda (E. carinicauda) is an economically important fishery species in China that has been found to exhibit increased body weight following Axn feeding as compared to a standard diet. The antioxidant, transcriptomic, and metabolomic analyses of the response of E. carinicauda after Axn feeding were investigated. Axn could reduce the content of malondialdehyde and increase the activities of various antioxidant enzymes, which also proved that axn can improve the antioxidant capacity Transcriptomic analysis suggested that synthesis and secretion of immune proteins, cytoskeleton structure, and apoptosis signaling were altered after Axn feeding. The metabolic response to axn mainly includes the up regulation of different amino acids and the change of unsaturated fatty acids. Combined transcriptomic and metabolomic data indicated that amino acid metabolic pathways were upregulated in the muscles after Axn feeding. For good measure, energy metabolism pathways were upregulated in the muscles to improve ATP and unsaturated fatty acid production. This study provides key information to increase our understanding of the effects of Axn in shrimp.
Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling
Authors: Thiemann Ellen , Schwaerzer Gerburg K. , Evangelakos Ioannis , Fuh Marceline M. , Jaeckstein Michelle Y. , Behrens Janina , Nilsson Stefan K. , Kumari Manju , Scheja Ludger , Pfeifer Alexander , Heeren Joerg , Heine Markus
Published: March 2022

Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis. By metabolic studies we found that cold-induced triglyceride uptake into BAT, lipoprotein disposal, glucose uptake and adaptive thermogenesis were not impaired in mice lacking Lpl exclusively in endothelial cells. This finding may be explained by a compensatory upregulation in the expression of adipocyte-derived Lpl and endothelial lipase (Lipg).
Non-destructive Storage Time Prediction of Newhall Navel Oranges Based on the Characteristics of Rind Oil Glands
Authors: Gao Shumin , Kang Hanwen , An Xiaosong , Cheng Yunjiang , Chen Hong , Chen Yaohui , Li Shanjun
Published: March 2022

How to non-destructively and quickly estimate the storage time of citrus fruit is necessary and urgent for freshness control in the fruit market. As a feasibility study, we present a non-destructive method for storage time prediction of Newhall navel oranges by investigating the characteristics of the rind oil glands in this paper. Through the observation using a digital microscope, the oil glands were divided into three types and the change of their proportions could indicate the rind status as well as the storage time. Images of the rind of the oranges were taken in intervals of 10 days for 40 days, and they were used to train and test the proposed prediction models based on K-Nearest Neighbors (KNN) and deep learning algorithms, respectively. The KNN-based model demonstrated explicit features for storage time prediction based on the gland characteristics and reached a high accuracy of 93.0%, and the deep learning-based model attained an even higher accuracy of 96.0% due to its strong adaptability and robustness. The workflow presented can be readily replicated to develop non-destructive methods to predict the storage time of other types of citrus fruit with similar oil gland characteristics in different storage conditions featuring high efficiency and accuracy.
Ultrasonic Waves Regulate Antioxidant Defense and Gluconeogenesis to Improve Germination From Naturally Aged Soybean Seeds
Authors: Huang Yutao , Mei Gaofu , Fu Xujun , Wang Yang , Ruan Xiaoli , Cao Dongdong
Published: March 2022

Soybean seeds contain substantial triacylglycerols and fatty acids that are prone to oxidation during storage, contributing to the dramatic deterioration of seed vigor. This study reports an ultrasonic waves treatment (UWT), which is a physical method capable of promoting the germination ability of the aged soybean seeds by regulating the antioxidant defense and gluconeogenesis. Germination test revealed that UWT significantly increased the germination rate and seedlings’ establishment of the soybean seeds stored for 12 months, although insignificantly impacting the vigor of fresh (stored for 1 month) and short-term stored (for 6 months) seeds. Further biochemical analysis revealed that UWT decreased the hydrogen peroxide (H2O2), O2⋅–, and malondialdehyde contents in the aged soybean seeds during early germination. Consistently, UWT prominently elevated the activities of superoxide dismutase, catalase, and acetaldehyde dehydrogenase, and also the corresponding gene expressions. Besides, the soluble sugar content of UWT was significantly higher than that of the untreated aged seeds. Analysis of enzyme activity showed UWT significantly upregulated the activities of several key enzymes in gluconeogenesis and the transcription levels of corresponding genes. Moreover, UWT enhanced the invertase activity within aged seeds, which was responsible for catalyzing sucrose hydrolysis for forming glucose and fructose. In summary, UWT improved germination and seedlings establishment of aged soybean seeds by regulating antioxidant defense and gluconeogenesis. This study expands the application of ultrasonication in agricultural production and further clarifies the physiological and molecular mechanisms of the aged seed germination, aiming to provide theoretical and practical guidance for seed quality and safety.
Use of Urban Residential Community Parks for Stress Management During the COVID-19 Lockdown Period in China
Authors: Kang Ni , Bell Simon , Ward Thompson Catharine , Zheng Mengmeng , Xu Ziwei , Sun Ziwen
Published: March 2022

During the pandemic lockdown period, residents had to stay at home and increased stress and other mental health problems have been associated with the lockdown period. Since most public parks were closed, community parks within gated residential areas became the most important green space in Chinese cities, and the use of such space might help to reduce the residents’ stress levels. This study aimed to investigate to what extent urban residents in China used community parks, engaged in outdoor activity during the lockdown period (23 January–8 April 2020) and if the use of such spaces helped to reduce their stress levels. An online questionnaire survey (n = 1342) was carried out from 23 March to 23 April 2020. Ordinary Least Squares regression was used to analyse the association between community park use, outdoor activity, willingness to engage in outdoor activity, and stress level. All results have been further analysed by two-sampled t-test to explore the difference between young and old age groups. We found that the overall self-reported stress level of the respondents was relatively moderate during the lockdown period. Respondents had generally reduced their use of community parks and engagement in outdoor activity. There was no significant association between stress level and the use of community parks or the engagement in outdoor activities. However, we found that older people showed much lower stress levels, used community parks more frequently, and engaged in more outdoor activities than younger adults. The findings suggest that outdoor activities and spatial characteristics in urban China differ from Western studies and advance the need to integrate the stress management role of community parks with urban green space policy to optimise the use of community parks blended in with everyday life, particularly during the lockdown period.
Sharing Online Health Information With Physicians: Understanding the Associations Among Patient Characteristics, Directness of Sharing, and Physician-Patient Relationship
Authors: Li Siyue , Wang Kexin
Published: March 2022

Patients increasingly share online health information with their physicians. However, few studies have investigated factors that may facilitate or inhibit such sharing and subsequent impact on physician-patient relationship. This study conducted a cross-sectional survey among 818 Chinese patients to examine if two patient characteristics -communication apprehension and eHealth literacy- influence their ways of sharing online health information with physicians and subsequently impact physician-patient relationship. The results showed that a majority of surveyed participants searched health information online, and about half of them used such information during their doctor visits. Less apprehensive patients tend to share the information with their physicians more directly, which can positively affect perceived physician reactions and patient satisfaction. eHealth literacy, however, is not found to be associated with patients’ sharing of online information with physicians. This study underscores the importance of identifying patient characteristic’s role in patient-physician interaction.
Does Public Health Influence Economic Performance? Investigating the Role of Governance and Greener Energies for the Case of China
Authors: Huang Shaojie , Zhou Tiansong , Xu Chengying , Zheng Jiahui
Published: March 2022

In the last few decades, the world has faced some natural issues, due to which economic growth faces a severe threat. Natural disasters like pandemic outbreaks and man-made disasters like pollution emissions are very frequent in the current times, which also influenced the economic growth, where the institutes could play a primary role in economic growth stimulation. This study aims to analyze the association of public health expenditures, institutional quality, renewable energy, and economic performance in China. This study uses quarterly data covering the period from 1996Q1 to 2020Q4 and employs various time-series estimating approaches. The Augmented Dickey-Fuller estimates asserted that all the variables are stationary at first difference. Also, the Bayer-Hanck combined cointegration validates that all the variables are cointegrated. Employing the three long-run estimators, i.e., Fully Modified Ordinary Least Square, Dynamic Ordinary Least Square, and canonical cointegrating regression, the results asserted public health expenditures and institutional quality (including government efficiency and political stability) significantly enhances economic performance in China. Whereas two indicators of corruption control and regulatory quality do not play any significant role in promoting the economic performance of China. On the contrary, renewable energy is found negatively associated with economic performance. Also, the Pair-wise Granger causality validates mixed causal associations between the study variables. As a developing and fossil energy-dependent economy, this study provides relevant policy implications for maintaining economic growth and rebalancing economic performance in China.
The Upsurge of Impact Factors in Pediatric Journals Post COVID-19 Outbreak: A Cross-Sectional Study
Authors: Mondal Pritish , Mazur Lauren , Su Lilly , Gope Suparna , Dell Esther
Published: March 2022

Background

Impact factor (IF) is a quantitative tool designed to evaluate scientific journals' excellence. There was an unprecedented upsurge in biomedical journals' IF in 2020, perhaps contributed by the increased number of publications since the COVID-19 outbreak. We conducted a cross-sectional study (2018–2020) to analyze recent trends in standard bibliometrics (IF, Eigenfactor, SNIP) of pediatric journals. We also estimated reference and publication counts of biomedical journals since publication volume determines the number of citations offered and IF.

Methods

Various bibliometrics of pediatric journals and reference/publication volumes of biomedical journals were compared between 2020 vs. 2019 and 2019 vs. 2018. We also compared open access (OA) and subscription journals' trends. Finally, we estimated IF changes in the journals of a different specialty, pulmonology.

Results

The study included 164 pediatric and 4,918 biomedical journals (OA = 1,473, subscription = 3,445). Pediatric journals' IFs had increased significantly in 2020 [median (IQR) = 2.35 (1.34)] vs. 2019 [1.82 (1.22)] (Wilcoxon: p-value < 0.001). IFs were unchanged between 2018 and 2019. Eigenfactor remained stable between 2018 and 2020, while SNIP increased progressively. Reference/publication volumes of biomedical journals escalated between 2018 and 2020, and OA journals experienced faster growth than subscription journals. IFs of pulmonary journals also increased considerably in 2020 vs. 2019.

Conclusions

We report an upsurge in pediatric journals' IF, perhaps contributed by a sudden increase in publication numbers in 2020. Therefore, considering this limitation, IF should be cautiously used as the benchmark of excellence. Unlike IF, Eigenfactor remained stable between 2018 and 2020. Similar changes in IF were also observed among the journals of another specialty, pulmonology.
Microorganisms Floating Through the Air
Authors: Tignat-Perrier Romie , Técher Nathalie , Vogel Timothy M. , Larose Catherine , Dommergue Aurélien
Published: March 2022

Would you believe us if we told you that, when you breathe in, you inhale thousands of microorganisms with every breath. Although this might sound scary, be assured that they are safe for your health. These airborne microorganisms, too small to see with the naked eye, consist of many different species. Who are they? Where do they come from? What do they do in the air? These are some of the questions that we answer in this article, although many questions about airborne microorganisms remain to be explored.
Harnessing Fe3O4 Screen-Printed Modified Electrode Sensor for Detecting Epinephrine in Buff Orpington Rooster and Rhodes Island White Broiler
Authors: Fayemi Omolola E. , Elugoke Saheed E. , Dina Oluwole , Mwanza Mulunda , Fayemi Peter O.
Published: March 2022

Nano-scale detection and characterization of neurotransmitters from real samples is a novel analytical technique with multiple applications in the field of nano-biotechnology. This in-situ electrochemical sensing tool has growing advantages of high reproducibility, rapid response, superior sensitivity, selectivity, accuracy, and miniaturization. A screen-printed iron oxide (Fe3O4) modified electrode was harnessed in this study for detecting epinephrine (EP), a chemical messenger or signalling neuro transmitting molecule, from two breeds of chickens. The fabricated sensor was used for the analysis of EP in the real and unspiked samples. UV-visible spectroscopy, Fourier-Transform infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), and Scanning Electron Microscopy (SEM) were used for characterizing the surface of nanoparticles prior to modification of screen-printed silver electrode (SPSE). The XRD diffractogram of Fe3O4 nanoparticles showed peaks at 30.1°, 35.7°, 43.3°, 53.9°, 57.5°, and 63.0°, corresponding to Miller indices of 220, 311, 400, 422, 511, and 440, respectively. This diffraction pattern indicates that the Fe3O4 nanoparticles have a spinel structure. Simultaneous detection of EP in the presence of ascorbic acid was obtained from Fe3O4 electrode. Further result shows a corresponding rise in oxidation peak current (Ipa) of EP with an increase in its concentration and scan rate of 25–400 mVs−1 confirming catalytic properties of the modified electrode towards EP. Our findings demonstrate that the fabricated sensor used for detecting EP in blood serum, breast muscle, and visceral organs of both chicken breeds produced better recovery.
Nitrogen and Phosphorus Fertilizers Improve Growth and Leaf Nutrient Composition of Moringa oleifera
Authors: Sokombela Asanda , Eiasu Bahlebi K. , Nyambo Patrick
Published: March 2022

Establishing the appropriate agronomic practices like fertilizer application is important for maximizing yield and improving nutritional quality of moringa (Moringa oleifera) leaves. The objective of the presented study was to determine the effects of nitrogen and phosphorus fertilizer rates on plant growth performance and leaf nutrient composition of moringa. The experiment was a 4 × 3 factorial, with four nitrogen levels (100, 200, 300, and 400 kg ha−1) and three levels of phosphorus (40, 80 and 120 kg ha−1). The experiment was laid out as randomized complete block design (RCBD), treatments were replicated four times. Twelve weeks after planting, the moringa trees treated with 100 kg N ha−1 and 80 kg P ha−1 were significantly taller by 46.8% than trees supplied with 400 kg N ha−1 and 120 kg P ha−1. Similarly, trees that received 100 kg N ha−1 and 80 kg P ha−1, and those treated with 200 kg N ha−1 and 80 kg P ha−1 had significantly greater stem diameter (>36%) compared to moringa trees that received 400 kg N ha−1 and 40 kg P ha−1. Crude protein was significantly higher by 26.3% in the 400 kg N ha−1 and 120 kg P ha−1 treatment combination than that of the 100 kg N ha−1 and 40 kg P ha−1 treatment combinations. Moringa trees that received 100 kg N ha−1 and 40 kg P ha−1 had the highest neutral detergent fiber content (30.71%), while the trees that received 400 kg N ha−1 and 120 kg P ha−1 had the lower neutral detergent fiber content of 22.77%. Based on the study, the combination of 100 kg N ha−1 and 80 kg P ha−1 can be recommended for maximum yield and nutritional content of moringa leaves.
A Multitask Learning Framework for Abuse Detection and Emotion Classification
Authors: Huang Yucheng , Song Rui , Giunchiglia Fausto , Xu Hao
Published: March 2022

The rapid development of online social media makes abuse detection a hot topic in the field of emotional computing. However, most natural language processing (NLP) methods only focus on linguistic features of posts and ignore the influence of users’ emotions. To tackle the problem, we propose a multitask framework combining abuse detection and emotion classification (MFAE) to expand the representation capability of the algorithm on the basis of the existing pretrained language model. Specifically, we use bidirectional encoder representation from transformers (BERT) as the encoder to generate sentence representation. Then, we used two different decoders for emotion classification and abuse detection, respectively. To further strengthen the influence of the emotion classification task on abuse detection, we propose a cross-attention (CA) component in the decoder, which further improves the learning effect of our multitask learning framework. Experimental results on five public datasets show that our method is superior to other state-of-the-art methods.
Boosting Iris Recognition by Margin-Based Loss Functions
Authors: Alinia Lat Reihan , Danishvar Sebelan , Heravi Hamed , Danishvar Morad
Published: March 2022

In recent years, the topic of contactless biometric identification has gained considerable traction due to the COVID-19 pandemic. One of the most well-known identification technologies is iris recognition. Determining the classification threshold for large datasets of iris images remains challenging. To solve this issue, it is essential to extract more discriminatory features from iris images. Choosing the appropriate loss function to enhance discrimination power is one of the most significant factors in deep learning networks. This paper proposes a novel iris identification framework that integrates the light-weight MobileNet architecture with customized ArcFace and Triplet loss functions. By combining two loss functions, it is possible to improve the compactness within a class and the discrepancies between classes. To reduce the amount of preprocessing, the normalization step is omitted and segmented iris images are used directly. In contrast to the original SoftMax loss, the EER for the combined loss from ArcFace and Triplet is decreased from 1.11% to 0.45%, and the TPR is increased from 99.77% to 100%. In CASIA-Iris-Thousand, EER decreased from 4.8% to 1.87%, while TPR improved from 97.42% to 99.66%. Experiments have demonstrated that the proposed approach with customized loss using ArcFace and Triplet can significantly improve state-of-the-art and achieve outstanding results.
Digital Technologies Determination Effectiveness for the Productivity of Organic Winter Wheat Production in Low Soil Performance Indicator
Authors: Astrauskas Paulius , Staugaitis Gediminas
Published: March 2022

The most important aspect of precision farming is the prediction of crop yield and quality. Digital technologies (soil maps and combine harvester with telemetry functions) were used to determinate the yield of organically grown winter wheat (variety Skagen) in two fields of 18.8 and 4.5 ha in Lithuanian regional conditions, in an area classified as low-performance for farming. The objective of the research was to determine the effectiveness of digital technologies (soil maps and combine harvester with telemetry functions) in assessment of the dynamics of soil pH, P2O5, and K2O, humus and organic winter wheat (variety Skagen) productivity, and grain crude-protein dependence in low-performance soils. Haplic Luvisol soils predominated, while Eutric Gleysols, Haplic Arenosols, and Eutric Planosols soils intervened in smaller areas, and the granulometric composition of the soil in the arable layer and the subsoil varied from sand to sandy loam, loam, and silt loam. In the sandy areas of Haplic Arenosols and in the lower parts of the field, where Eutric Gleysols, intervened in predominant Haplic Luvisols soils, winter wheat crude protein content and grain yield were lower. The biggest grain yield of 6.95 t ha−1 was obtained in Haplic Luvisols soils. Crude protein of winter wheat grains varied from 9.70 to 13.34%. Although both technologies reflected the non-uniform yields of the fields and correlation between them well, the information on the soil cover of the field better explained the reasons for lower yields. In the case of this research, sand inclusions and lower areas in winter wheat fields, causing plants to soak during winter, were identified. The combination of two digital technologies (soil maps and combine harvester with telemetry functions) made it possible to determine yields accurately, and quickly. Moreover, there is a need, in the future, to evaluate the reasons for yield variation and address changes in yields due to the improvement of certain low-performance soil areas. The complex use of these technologies can be beneficial in terms of labour and economy. However, the accurate benefit of labour time and economic should be investigated.
lnc-IL7R Expression Reflects Physiological Pulmonary Function and Its Aberration Is a Putative Indicator of COPD
Authors: Bamodu Oluwaseun Adebayo , Wu Sheng-Ming , Feng Po-Hao , Sun Wei-Lun , Lin Cheng-Wei , Chuang Hsiao-Chi , Ho Shu-Chuan , Chen Kuan-Yuan , Chen Tzu-Tao , Tseng Chien-Hua , Liu Wen-Te , Lee Kang-Yun
Published: March 2022

Despite rapidly evolving pathobiological mechanistic demystification, coupled with advances in diagnostic and therapeutic modalities, chronic obstructive pulmonary disease (COPD) remains a major healthcare and clinical challenge, globally. Further compounded by the dearth of available curative anti-COPD therapy, it is posited that this challenge may not be dissociated from the current lack of actionable COPD pathognomonic molecular biomarkers. There is accruing evidence of the involvement of protracted ‘smoldering’ inflammation, repeated lung injury, and accelerated lung aging in enhanced predisposition to or progression of COPD. The relatively novel uncharacterized human long noncoding RNA lnc-IL7R (otherwise called LOC100506406) is increasingly designated a negative modulator of inflammation and regulator of cellular stress responses; however, its role in pulmonary physiology and COPD pathogenesis remains largely unclear and underexplored. Our previous work suggested that upregulated lnc-IL7R expression attenuates inflammation following the activation of the toll-like receptor (TLR)-dependent innate immune system, and that the upregulated lnc-IL7R is anti-correlated with concomitant high PM2.5, PM10, and SO2 levels, which is pathognomonic for exacerbated/aggravated COPD in Taiwan. In the present study, our quantitative analysis of lnc-IL7R expression in our COPD cohort (n = 125) showed that the lnc-IL7R level was significantly correlated with physiological pulmonary function and exhibited COPD-based stratification implications (area under the curve, AUC = 0.86, p < 0.001). We found that the lnc-IL7R level correctly identified patients with COPD (sensitivity = 0.83, specificity = 0.83), precisely discriminated those without emphysematous phenotype (sensitivity = 0.48, specificity = 0.89), and its differential expression reflected disease course based on its correlation with the COPD GOLD stage (r = −0.59, p < 0.001), %LAA-950insp (r = −0.30, p = 0.002), total LAA (r = −0.35, p < 0.001), FEV1(%) (r = 0.52, p < 0.001), FVC (%) (r = 0.45, p < 0.001), and post-bronchodilator FEV1/FVC (r = 0.41, p < 0.001). Consistent with other data, our bioinformatics-aided dose–response plot showed that the probability of COPD decreased as lnc-IL7R expression increased, thus, corroborating our posited anti-COPD therapeutic potential of lnc-IL7R. In conclusion, reduced lnc-IL7R expression not only is associated with inflammation in the airway epithelial cells but is indicative of impaired pulmonary function, pathognomonic of COPD, and predictive of an exacerbated/ aggravated COPD phenotype. These data provide new mechanistic insights into the ailing lung and COPD progression, as well as suggest a novel actionable molecular factor that may be exploited as an efficacious therapeutic strategy in patients with COPD.
The Cytogenetic Landscape of Pediatric Chronic Myeloid Leukemia Diagnosed in Chronic Phase
Authors: Karow Axel , Göhring Gudrun , Sembill Stephanie , Lutterloh Friederike , Neuhaus Fina , Callies Sara , Schirmer Elke , Wotschofsky Zofia , Roche-Lancaster Oisin , Suttorp Meinolf , Krumbholz Manuela , Metzler Markus
Published: March 2022

Philadelphia chromosome-positive chronic myeloid leukemia (CML) is cytogenetically characterized by the classic translocation t(9;22)(q34;q11), whereas additional non-Philadelphia aberrations (nPhAs) have been studied extensively in adult patients with CML, knowledge on nPhAs in pediatric patients with CML is still sparse. Here, we have determined nPhAs in a cohort of 161 patients younger than 18 years diagnosed with chronic phase CML and consecutively enrolled in the German national CML-PAED-II registry. In 150 cases (93%), an informative cytogenetic analysis had been performed at diagnosis. In total, 21 individuals (13%) showed nPhAs. Of these, 12 (8%) had a variant translocation, 4 (3%) additional chromosomal aberrations (ACAs) and 5 (3%) harbored a complex karyotype. Chromosome 15 was recurrently involved in variant translocations. No significant impact of the cytogenetic subgroup on the time point of cytogenetic response was observed. Patients with a complex karyotype showed an inferior molecular response compared to patients carrying the classic translocation t(9;22)(q34;q11), variant translocations or ACAs. No significant differences in the probability of progression-free survival and overall survival was found between patients with nPhAs and patients with the classic Philadelphia translocation only. Our results highlight the distinct biology of pediatric CML and underline the need for joint international efforts to acquire more data on the disease pathogenesis in this age group.
Health-Related Quality of Life in Metastatic Colorectal Cancer Patients Treated with Curative Resection and/or Local Ablative Therapy or Systemic Therapy in the Finnish RAXO-Study
Authors: Lehtomäki Kaisa , Stedt Hanna P. , Osterlund Emerik , Muhonen Timo , Soveri Leena-Maija , Halonen Päivi , Salminen Tapio K. , Kononen Juha , Kallio Raija , Ålgars Annika , Heervä Eetu , Lamminmäki Annamarja , Uutela Aki , Nordin Arno , Lehto Juho , Saarto Tiina , Sintonen Harri , Kellokumpu-Lehtinen Pirkko-Liisa , Ristamäki Raija , Glimelius Bengt , Isoniemi Helena , Osterlund Pia
Published: March 2022

Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89–0.91 with the 15D, 0.85–0.87 with the EQ-5D, 68–80 with the EQ-5D-VAS, and 68–79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors’ well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.
Blocking Gi/o-Coupled Signaling Eradicates Cancer Stem Cells and Sensitizes Breast Tumors to HER2-Targeted Therapies to Inhibit Tumor Relapse
Authors: Lyu Cancan , Ye Yuanchao , Weigel Ronald J. , Chen Songhai
Published: March 2022

Cancer stem cells (CSCs) are a small subpopulation of cells within tumors that are resistant to anti-tumor therapies, making them a likely origin of tumor relapse after treatment. In many cancers including breast cancer, CSC function is regulated by G protein-coupled receptors (GPCRs), making GPCR signaling an attractive target for new therapies designed to eradicate CSCs. Yet, CSCs overexpress multiple GPCRs that are redundant in maintaining CSC function, so it is unclear how to target all the various GPCRs to prevent relapse. Here, in a model of HER2+ breast cancer (i.e., transgenic MMTV-Neu mice), we were able to block the tumorsphere- and tumor-forming capability of CSCs by targeting GPCRs coupled to Gi/o proteins (Gi/o-GPCRs). Similarly, in HER2+ breast cancer cells, blocking signaling downstream of Gi/o-GPCRs in the PI3K/AKT and Src pathways also enhanced HER2-targeted elimination of CSCs. In a proof-of-concept study, when CSCs were selectively ablated (via a suicide gene construct), loss of CSCs from HER2+ breast cancer cell populations mimicked the effect of targeting Gi/o-GPCR signaling, suppressing their capacity for tumor initiation and progression and enhancing HER2-targeted therapy. Thus, targeting Gi/o-GPCR signaling in HER2+ breast cancer is a promising approach for eradicating CSCs, enhancing HER2+ targeted therapy and blocking tumor reemergence.
Physical Activity and Sedentary Behavior in Relation to Cancer Survival: A Narrative Review
Authors: Jochem Carmen , Leitzmann Michael
Published: March 2022

From a public health perspective, cancer is a major issue, and it contributes to a high economic and societal burden. Lifestyle-associated risk factors play a crucial role in cancer prevention. The present narrative review aims to summarize the existing evidence on the relationship of physical activity and sedentary behavior to cancer survival, including the evidence on mortality and other health-related outcomes. There is strong evidence that physical activity before, during, and after cancer diagnosis improves outcomes for breast and colorectal cancers. In addition, there is emerging evidence that reduced levels of sedentary behavior in cancer survivors are associated with improved outcomes. Future studies are needed to strengthen the evidence and to provide details on additional cancer sites. In the meantime, existing recommendations for physical activity and sedentary behavior in cancer survivors should be followed to improve the health status of cancer survivors.
MUC1 (CA27.29) before and after Chemotherapy and Prognosis in High-Risk Early Breast Cancer Patients
Authors: Huebner Hanna , Häberle Lothar , Müller Volkmar , Schrader Iris , Lorenz Ralf , Forstbauer Helmut , Fink Visnja , Schochter Fabienne , Bekes Inga , Mahner Sven , Jückstock Julia , Nabieva Naiba , Schneeweiss Andreas , Tesch Hans , Brucker Sara , Blohmer Jens-Uwe , Fehm Tanja , Heinrich Georg , Rezai Mahdi , Beckmann Matthias , Fasching Peter , Janni Wolfgang , Rack Brigitte
Published: March 2022

Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.
Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Umutlu Lale , Kirchner Julian , Bruckmann Nils-Martin , Morawitz Janna , Antoch Gerald , Ting Saskia , Bittner Ann-Kathrin , Hoffmann Oliver , Häberle Lena , Ruckhäberle Eugen , Catalano Onofrio Antonio , Chodyla Michal , Grueneisen Johannes , Quick Harald H. , Fendler Wolfgang P. , Rischpler Christoph , Herrmann Ken , Gibbs Peter , Pinker Katja
Published: March 2022

Background: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. Methods: A total of 73 female patients (mean age 49 years; range 27–77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2− group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2− receptor status.
A Nanoparticle’s Journey to the Tumor: Strategies to Overcome First-Pass Metabolism and Their Limitations
Authors: Milligan Joshua J. , Saha Soumen
Published: March 2022

Nanomedicines represent the cutting edge of today’s cancer therapeutics. Seminal research decades ago has begun to pay dividends in the clinic, allowing for the delivery of cancer drugs with enhanced systemic circulation while also minimizing off-target toxicity. Despite the advantages of delivering cancer drugs using nanoparticles, micelles, or other nanostructures, only a small fraction of the injected dose reaches the tumor, creating a narrow therapeutic window for an otherwise potent drug. First-pass metabolism of nanoparticles by the reticuloendothelial system (RES) has been identified as a major culprit for the depletion of nanoparticles in circulation before they reach the tumor site. To overcome this, new strategies, materials, and functionalization with stealth polymers have been developed to improve nanoparticle circulation and uptake at the tumor site. This review summarizes the strategies undertaken to evade RES uptake of nanomedicines and improve the passive and active targeting of nanoparticle drugs to solid tumors. We also outline the limitations of current strategies and the future directions we believe will be explored to yield significant benefits to patients and make nanomedicine a promising treatment modality for cancer.
Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study
Authors: Bauckneht Matteo , Rebuzzi Sara Elena , Ponzano Marta , Borea Roberto , Signori Alessio , Frantellizzi Viviana , Lodi Rizzini Elisa , Mascia Manlio , Lavelli Valentina , Miceli Alberto , De Feo Maria Silvia , Pisani Antonio Rosario , Nuvoli Susanna , Tripoli Vincenzo , Morganti Alessio Giuseppe , Mammucci Paolo , Caponnetto Salvatore , Mantica Guglielmo , Di Nicola Angelo Domenico , Villano Carlo , Cindolo Luca , Morbelli Silvia , Sambuceti Gianmario , Fanti Stefano , Costa Renato Patrizio , Spanu Angela , Rubini Giuseppe , Monari Fabio , De Vincentis Giuseppe , Fornarini Giuseppe
Published: March 2022

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.
Predicting Long-Term Prognoses and Grading Platinum Sensitivity Using a Novel Progression-Free Interval Criterion in Ovarian Clear Cell Carcinoma: A Multi-Institutional Cohort Study
Authors: Chou Cheng-Yang , Cheng Wen-Fang , Chen Min-Yu , Lin Hao , Ho Chih-Ming , Hung Yao-Ching , Huang Lee-Wen , Wang Po-Hui , Yu Mu-Hsien , Huang Yu-Fang
Published: March 2022

This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemo-response independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. A PFI of <7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and/or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.