bluuebunny/crossref_metadata_2025 huggingface dataset:
THE GENRE FEATURES OF UKRAINIAN BAROQUE SERMON
Authors: Bomko Liliia
Published: February 2022

This paper is an attempt to comprehend the theoretical preconditions of the genre structure of the Ukrainian baroque sermon in the process of its formation and development starting from “Teaching Gospel” of the early baroque period written by Kyrylo Trankvilion Stavrovetskyi till the homiletic treatise “The Art or the Method of Composing the Sermon” by Ioanykii Galiatovskyi. The forms and principles of coexistence of two homiletical patterns, Greco-Slavic and Latin-Polish, are considered as a channel of rhetorical and stylistic changes that determine genre modifications and varieties. Viewed in this way, the author’s introductions, topics of sermons, and their consistency with different composite parts of the text give grounds to observe the consecutive actualization of the whole conception within the ambit of the whole book and individual sermon samples.

One of the key issues is the interaction of oral and written (book) forms of a sermon, which reveals a double level of communication with the recipient: listening and reading. This is demonstrated by the oral practices of preaching by Kyrylo Trankvilion Stavrovetskyi, Ioanykii Galiatovskyi, Antonii Radyvylovskyi, and Lazar Baranovych, on the one hand. On the other hand, in their collections of sermons named “Key of Understanding”, “Virgin Mary’s Garden”, “Spiritual Sword”, “Trumpets of Sermon Words”, the authors, in addition to the practical part, give some theoretical comments and reflections on their creative process, endowed with divine power.

The development of the theory of Ukrainian baroque preaching was greatly influenced by the homiletic treatise by Ioanykii Galiatovskyi “The Art or the Method of Composing the Sermon”, in which the author consistently elaborates the main issues concerning the theme, composition, examples, and amplification.
Türkiye’de Toplu Konut İdaresi (TOKİ) Kentsel Dönüşüm Uygulamalarında Kütüphanelerin Yeri
Authors: KÖSE Fatma Nur , AKKAYA Mehmet Ali
Published: February 2022

Toplumsal ve sosyal yaşamın bir parçası olan kentler, oluştukları andan itibaren toplumsal süreç ve değişkenlerini etkileyen ve onlardan en çok etkilenen unsurlardan biri olarak günümüzdeki formlarına ulaşmıştır. Özellikle Endüstri Devrimi, kentlerde sosyal, kültürel ve toplumsal birçok değişikliğin çıkış noktası olmuştur. Yaşanan değişim ise kent ve insan ilişkisini farklılaştırmış, kentleşme ve kentli olmak toplumsal yaşamın genel yönelime dönüşmüştür. Türkiye özelinde 1950’li yıllardan itibaren iç göç hareketleri ile birlikte nüfus kentlerde yoğunlaşmaya başlamış kentleşme hız kazanmış, kentler yaşamın her yönü üzerinde doğrudan etkili karmaşık ve dinamik sistemler haline dönüşmüşlerdir. Kentleşmenin hız kazanması ve kentlerde artan konut, alt yapı, ulaşım gibi teknik ve sosyo-kültürel problemler, kentsel dönüşüm kavramının ortaya çıkmasına ve önem kazanmasına neden olmuştur. Kentsel dönüşüm uygulamalarında gereken önemi bulamamış olmasına rağmen, kentlerin kültürel ve sosyal sorunlarını çözüme kavuşturacak en önemli unsurlardan biri de sosyal donatı alanlarıdır. Bilgi merkezlerinin en yaygın ve toplumsal anlamda en bilinen türü olan kütüphaneler, sosyal donatı alanlarının içerisinde yer almaktadır. Kent yaşamında, toplumsal ve kültürel uyum probleminin önüne geçerek ortak bir kent kültürünün benimsenmesini, sundukları hizmetlerle kentli olmayı ve kente uyum sağlamayı kolaylaştıran kütüphaneler kentsel dönüşüm projelerinde yeterince dikkate alınmamaktadır. Aynı zamanda çalışmanın hipotezini de oluşturan bu tablo, araştırmanın da çıkış noktasıdır. Bu çalışmada, Türkiye’de kentsel dönüşüm projelerinde sosyal donatı alanı olarak kütüphanelerin uygulama içerisindeki payının ortaya konması amaçlanmıştır. Söz konusu amaç doğrultusunda, ülkemizde kentsel dönüşüm projelerinin planlayıcısı ve yürütücüsü konumunda olan Toplu Konut İdaresi (TOKİ)’nin kamuoyu ile paylaştığı resmi bilgiler dikkate alınmış ve kentsel dönüşüm projeleri incelenmiştir. İncelemelerin ayrıntısı için veri ve belge analizinden yararlanılmıştır. Elde edilen verilere göre, Türkiye’de kentsel dönüşüm uygulamalarında (toplam 3.387 uygulama) sosyal donatı alanlarına yer verilse dâhi (%42,60), sosyal donatı unsuru olarak kütüphanelerin kentsel dönüşüm projeleri içerisindeki payı (%1,09) kabul edilebilir düzeyde değildir. Dünyada en yoğun kentsel dönüşüm uygulamasının yürütüldüğü ülkelerden biri olmamıza karşın, araştırma kapsamında elde edilen rakamlar ve ayrıntıları, dönüşüm uygulamalarında sosyal donatı alanlarının, özellikle de kütüphanelerin çok akla getirilmediğini ortaya koymaktadır. Sürecin tüm paydaşlarına çok yönlü sorumluluklarını anımsatmayı arzulayan çalışma, bu soruna dikkat çektiği ve sorunun çözümüne katkı sağladığı ölçüde başarılı olacaktır.
The Origins of Musical and Pedagogical Education in the Culture of the Ancient World
Authors:   Lugansk State Pedagogical University, Labintseva Larisa P.
Published: February 2022

The article examines the sources of development of musical-pedagogical education during the period of Ancient Greece and Rome. The author draws our attention to the fact that the main goal of musicalpedagogical education of that time was the self-determination of personality, visibility, consistency during the process of education and a concentric placement of the material. The basis for further development of the discipline of musical pedagogy became the stance that education and upbringing should correlate with the nature of the child’s soul.
Music in the Space of Metaphysics (by the Example of the World Philosophical Heritage)
Authors:   Institute of Music, Theater and Choreography, Herzen State Pedagogical University of Russia, Huang Zehuan , Wu Zhuofen ,   Institute of Music, Theater and Choreography, Herzen State Pedagogical University of Russia, Guo Shaoying ,   Institute of Music, Theater and Choreography, Herzen State Pedagogical University of Russia
Published: February 2022

The article comprehends the issue of music as a metaphysics which determines the optimal environment for the formation of a personality marked by spiritual self-standing. The authorial concept is built on the basis of world philosophical heritage represented by the achievements of the East and the West. Solving in a step-by-step manner the issues of the general and the special in music and philosophy, in teaching and in education, the authors focus their attention on revising the concepts of “the philosophy of education”, “the philosophy of art” and “the philosophy of music”. Putting forward the assumption that if the philosophy of music is an experience of spiritual comprehension of the composer’s creation as a process of meaning formation, and the philosophy of art as a whole appears as a practice aimed at awakening the human practice in a person, then the philosophy of education can be considered as the implementation of the indicated experience through each specific academic discipline. In the end, the authors conclude that the place and role of music in the formation of personality are determined not only by the goals of musical education, but are also directly related to the worldview orientation of the personality, laying the foundation for its holistic development and providing it with the opportunity to build its future according to the laws of harmony and beauty.
Development and Utilization of an Isolation Box Test to Characterize Personality Traits of Dairy Calves
Authors: Woodrum Setser Megan M. , Neave Heather W. , Vanzant Eric , Costa Joao H. C.
Published: February 2022

The use of an isolation box test (IBT) to characterize personality traits has been used in non-bovine species with success. We aimed to develop an IBT for dairy calves and determine if the behavioral responses to an IBT were associated with personality traits found from traditional tests (novel person, novel object, and a startle tests) and average daily gain (ADG; Kg/d) through weaning. Calf movement while in the IBT was measured via accelerometers attached to 5 locations on the exterior of the box. A total movement index (TMI) was calculated based on accelerometer readings during the IBT. We performed a principal component analysis on the traditional tests and identified 3 influential factors that we labeled as “fearful,” “bold,” and “active.” Calves were weighed biweekly to track liveweight ADG. Factor scores and ADG were regressed against TMI. A significant negative association was found between the TMI and the factor “active,” indicating the validity of IBT as a tool for assessing some personality traits of dairy calves. Furthermore, TMI had a positive association with ADG through the entire experimental period and thus has potential to help predict performance through weaning. IBT has potential to be used as a personality test in research scenarios. Further development is needed to produce an IBT that would be appropriate to measure animals' responses reliably in production settings. An automated test that can accommodate a wide range of ages and developing a computer learning model to interpret output from the IBT would be a possible option to do so.
Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms
Authors: Nupur Neh , Joshi Srishti , Gulliarme Davy , Rathore Anurag S.
Published: February 2022

Biopharmaceuticals are one of the fastest-growing sectors in the biotechnology industry. Within the umbrella of biopharmaceuticals, the biosimilar segment is expanding with currently over 200 approved biosimilars, globally. The key step towards achieving a successful biosimilar approval is to establish analytical and clinical biosimilarity with the innovator. The objective of an analytical biosimilarity study is to demonstrate a highly similar profile with respect to variations in critical quality attributes (CQAs) of the biosimilar product, and these variations must lie within the range set by the innovator. This comprises a detailed comparative structural and functional characterization using appropriate, validated analytical methods to fingerprint the molecule and helps reduce the economic burden towards regulatory requirement of extensive preclinical/clinical similarity data, thus making biotechnological drugs more affordable. In the last decade, biosimilar manufacturing and associated regulations have become more established, leading to numerous approvals. Biosimilarity assessment exercises conducted towards approval are also published more frequently in the public domain. Consequently, some technical advancements in analytical sciences have also percolated to applications in analytical biosimilarity assessment. Keeping this in mind, this review aims at providing a holistic view of progresses in biosimilar analysis and approval. In this review, we have summarized the major developments in the global regulatory landscape with respect to biosimilar approvals and also catalogued biosimilarity assessment studies for recombinant DNA products available in the public domain. We have also covered recent advancements in analytical methods, orthogonal techniques, and platforms for biosimilar characterization, since 2015. The review specifically aims to serve as a comprehensive catalog for published biosimilarity assessment studies with details on analytical platform used and critical quality attributes (CQAs) covered for multiple biotherapeutic products. Through this compilation, the emergent evolution of techniques with respect to each CQA has also been charted and discussed. Lastly, the information resource of published biosimilarity assessment studies, created during literature search is anticipated to serve as a helpful reference for biopharmaceutical scientists and biosimilar developers.
Biomimetic Cucurbitacin B-Polydopamine Nanoparticles for Synergistic Chemo-Photothermal Therapy of Breast Cancer
Authors: Leng Junke , Dai Xiaofeng , Cheng Xiao , Zhou Hao , Wang Dong , Zhao Jing , Ma Kun , Cui Changhao , Wang Li , Guo Zhaoming
Published: February 2022

Breast cancer is the most common malignant tumor in women. Researchers have found that the combined use of multiple methods to treat tumors is a promising strategy. Here, we have developed a biomimetic nano-platform PDA@MB for tumor targeted photothermal therapy (PTT) combined with chemotherapy. The 4T1 cell membrane loaded with cucurbitacin B (CuB) was used to coat polydopamine (PDA) nanoparticles, which gave PDA@MB nanoparticles the ability to target tumors and escape immune cells from phagocytosis. PDA@MB showed excellent photothermal performance including high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. The high temperature ruptured the PDA@MB membrane to release CuB, which changed the tumor hypoxic environment, down-regulated the FAK/MMP signaling pathway, and significantly inhibited the metastasis and proliferation of tumor cells. The results of in vivo experiments indicated that the tumor growth of the 4T1 mouse tumor model was significantly inhibited. Additionally, toxicity studies showed that PDA@MB had good biocompatibility and safety. In conclusion, this study provides a promising chemo-photothermal therapy (CPT) nano-platform for precise and effective breast cancer therapy.
Functions of RNF Family in the Tumor Microenvironment and Drugs Prediction in Grade II/III Gliomas
Authors: Zhang Jingwei , Wang Zeyu , Zhang Hao , Dai Ziyu , Liang Xisong , Li Shuwang , Zhang Xun , Liu Fangkun , Liu Zhixiong , Yang Kui , Cheng Quan
Published: February 2022

Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.
Geroprotectors and Skeletal Health: Beyond the Headlines
Authors: Rayson Alexandra , Boudiffa Maya , Naveed Maneeha , Griffin Jon , Dall’Ara Enrico , Bellantuono Ilaria
Published: February 2022

Osteoporosis and osteoarthritis are the most common age-related diseases of the musculoskeletal system. They are responsible for high level of healthcare use and are often associated with comorbidities. Mechanisms of ageing such as senescence, inflammation and autophagy are common drivers for both diseases and molecules targeting those mechanisms (geroprotectors) have potential to prevent both diseases and their co-morbidities. However, studies to test the efficacy of geroprotectors on bone and joints are scant. The limited studies available show promising results to prevent and reverse Osteoporosis-like disease. In contrast, the effects on the development of Osteoarthritis-like disease in ageing mice has been disappointing thus far. Here we review the literature and report novel data on the effect of geroprotectors for Osteoporosis and Osteoarthritis, we challenge the notion that extension of lifespan correlates with extension of healthspan in all tissues and we highlight the need for more thorough studies to test the effects of geroprotectors on skeletal health in ageing organisms.
Expanding of Life Strategies in Placozoa: Insights From Long-Term Culturing of Trichoplax and Hoilungia
Authors: Romanova Daria Y. , Nikitin Mikhail A. , Shchenkov Sergey V. , Moroz Leonid L.
Published: February 2022

Placozoans are essential reference species for understanding the origins and evolution of animal organization. However, little is known about their life strategies in natural habitats. Here, by maintaining long-term culturing for four species ofTrichoplaxandHoilungia, we extend our knowledge about feeding and reproductive adaptations relevant to the diversity of life forms and immune mechanisms. Three modes of population dynamics depended upon feeding sources, including induction of social behaviors, morphogenesis, and reproductive strategies. In addition to fission, representatives of all species produced “swarmers” (a separate vegetative reproduction stage), which could also be formed from the lower epithelium with greater cell-type diversity. We monitored the formation of specialized spheroid structures from the upper cell layer in aging culture. These “spheres” could be transformed into juvenile animals under favorable conditions. We hypothesize that spheroid structures represent a component of the innate immune defense response with the involvement of fiber cells. Finally, we showed that regeneration could be a part of the adaptive reproductive strategies in placozoans and a unique experimental model for regenerative biology.
Circulating TGF-β Pathway in Osteogenesis Imperfecta Pediatric Patients Subjected to MSCs-Based Cell Therapy
Authors: Infante Arantza , Cabodevilla Leire , Gener Blanca , Rodríguez Clara I.
Published: February 2022

Osteogenesis Imperfecta (OI) is a rare genetic disease characterized by bone fragility, with a wide range in the severity of clinical manifestations. The majority of cases are due to mutations in COL1A1 or COL1A2, which encode type I collagen. There is no cure for OI, and real concerns exist for current therapeutic approaches, mainly antiresorptive drugs, regarding their effectiveness and security. Safer and effective therapeutic approaches are demanded. Cell therapy with mesenchymal stem cells (MSCs), osteoprogenitors capable of secreting type I collagen, has been tested to treat pediatric OI with encouraging outcomes. Another therapeutic approach currently under clinical development focuses on the inhibition of TGF-β pathway, based on the excessive TGF-β signaling found in the skeleton of severe OI mice models, and the fact that TGF-β neutralizing antibody treatment rescued bone phenotypes in those OI murine models. An increased serum expression of TGF-β superfamily members has been described for a number of bone pathologies, but still it has not been addressed in OI patients. To delve into this unexplored question, in the present study we investigated serum TGF-β signalling pathway in two OI pediatric patients who participated in TERCELOI, a phase I clinical trial based on reiterative infusions of MSCs. We examined not only the expression and bioactivity of circulating TGF-β pathway in TERCELOI patients, but also the effects that MSCs therapy could elicit. Strikingly, basal serum from the most severe patient showed an enhanced expression of several TGF-β superfamily members and increased TGF-β bioactivity, which were modulated after MSCs therapy.
Non-Apoptotic Role of Apoptotic Caspases in the Drosophila Nervous System
Authors: Colon-Plaza Sarah , Su Tin Tin
Published: February 2022

An increasing number of studies demonstrate that cells can activate apoptotic caspases but not die and, instead, display profound changes in cellular structure and function. In this minireview, we will discuss observations in the nervous system of Drosophila melanogaster that illustrate non-apoptotic roles of apoptotic caspases. We will preface these examples with similar observations in other experimental systems and end with a discussion of how apoptotic caspase activity might be constrained to provide non-lethal functions without killing the cell.
Developmental Language Disorder as Syntactic Prediction Impairment
Authors: Hestvik Arild , Epstein Baila , Schwartz Richard G. , Shafer Valerie L.
Published: February 2022

We provide evidence that children with Developmental Language Disorder (DLD) are impaired in predictive syntactic processing. In the current study, children listened passively to auditorily-presented sentences, where the critical condition included an unexpected “filled gap” in the direct object position of the relative clause verb. A filled gap is illustrated by the underlined phrase in “The zebra that the hippo kissed the camel on the nose…”, rather than the expected “the zebra that the hippo kissed [e] on the nose”, where [e] denotes the gap. Brain responses to the filled gap were compared to a control condition using adverb-relative clauses with identical substrings: “The weekend that the hippo kissed the camel on the nose [e]…”. Here, the same noun phrase is not unexpected because the adverb gap occurs later in the structure. We hypothesized that a filled gap would elicit a prediction error brain signal in the form of an early anterior negativity, as we have previously observed in adults. We found an early (bilateral) anterior negativity to the filled gap in a control group of children with Typical Development (TD), but the children with DLD exhibited no brain response to the filled gap during the same early time window. This suggests that children with DLD fail to predict that a relativized object should correspond to an empty position after the relative clause verb, suggesting an impairment in predictive processing. We discuss how this lack of a prediction error signal can interact with language acquisition and result in DLD.
Challenges and Open Issues in Transcatheter Mitral Valve Implantation: Smooth Seas Do Not Make Skillful Sailors
Authors: Russo Giulio , Maisano Francesco , Massaro Gianluca , Terlizzese Giuseppe , Mariano Enrica , Bonanni Michela , Matteucci Andrea , Bezzeccheri Andrea , Benedetto Daniela , Chiricolo Gaetano , Martuscelli Eugenio , Sangiorgi Giuseppe Massimo
Published: February 2022

According to the European and American guidelines, surgery represents the treatment of choice for mitral valve (MV) disease. However, a number of patients are deemed unsuitable for surgery due to a prohibitive/high operative risk. In such cases, transcatheter therapies aiming at MV repair have been proven to be a valuable alternative and have been recently introduced in the latest American guidelines on valvular heart disease. Indeed, percutaneous repair techniques, particularly transcatheter edge-to-edge, have gained a broad experience and demonstrated to be safe and effective. However, given the complexity and heterogeneity of MV anatomy and pathology, transcatheter MV implantation (TMVI) has grown as a possible alternative to percutaneous MV repair. Current data about TMVI are still limited and come from different settings: valve-in-native MV, valve-in-valve (ViV), valve-in-ring (ViR), and valve-in-mitral annular calcification. Preliminary data are promising although several open issues still need to be addressed. This paper provides a comprehensive review of the available devices in the different clinical settings, to discuss potentialities, limitations, and future directions for TMVI.
Effects of Home-Based Baduanjin Exercise on Left Ventricular Remodeling in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial
Authors: Cai Yinhe , Kang Liang , Li Haiyi , Luo Yuan , Wen Junmao , Gong Zhaohui , Chu Qingmin , Qiu Yijun , Luo Chuanjin , Chen Keyu , Zhao Xinjun , Li Rong
Published: February 2022

Background

Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently.

Methods/Design

A single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation.

Discussion

This study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes.

Trial Registration

The Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298).

Dissemination

Our results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet.
Prediction of 2-Year Major Adverse Limb Event-Free Survival After Percutaneous Transluminal Angioplasty and Stenting for Lower Limb Atherosclerosis Obliterans: A Machine Learning-Based Study
Authors: Pan Tianyue , Jiang Xiaolang , Liu Hao , Liu Yifan , Fu Weiguo , Dong Zhihui
Published: February 2022

Background

The current scoring systems could not predict prognosis after endovascular therapy for peripheral artery disease. Machine learning could make predictions for future events by learning a specific pattern from existing data. This study aimed to demonstrate machine learning could make an accurate prediction for 2-year major adverse limb event-free survival (MFS) after percutaneous transluminal angioplasty (PTA) and stenting for lower limb atherosclerosis obliterans (ASO).

Methods

A lower limb ASO cohort of 392 patients who received PTA and stenting was split to the training set and test set by 4:1 in chronological order. Demographic, medical, and imaging data were used to build machine learning models to predict 2-year MFS. The discrimination and calibration of artificial neural network (ANN) and random forest models were compared with the logistic regression model, using the area under the receiver operating curve (ROCAUC) with DeLong test, and the calibration curve with Hosmer–Lemeshow goodness-of-fit test, respectively.

Results

The ANN model (ROCAUC = 0.80, 95% CI: 0.68–0.89) but not the random forest model (ROCAUC = 0.78, 95% CI: 0.66–0.87) significantly outperformed the logistic regression model (ROCAUC = 0.73, 95% CI: 0.60–0.83, P = 0.01 and P = 0.24). The ANN model the logistic regression model demonstrated good calibration performance (P = 0.73 and P = 0.28), while the random forest model showed poor calibration (P < 0.01). The calibration curve of the ANN model was visually the closest to the perfectly calibrated line.

Conclusion

Machine learning models could accurately predict 2-year MFS after PTA and stenting for lower limb ASO, in which the ANN model had better discrimination and calibration. Machine learning-derived prediction tools might be clinically useful to automatically identify candidates for PTA and stenting.
Exercise Systolic Reserve and Exercise Pulmonary Hypertension Improve Diagnosis of Heart Failure With Preserved Ejection Fraction
Authors: Verwerft Jan , Verbrugge Frederik H. , Claessen Guido , Herbots Lieven , Dendale Paul , Gevaert Andreas B.
Published: February 2022

Aims

Diastolic stress testing (DST) is recommended to confirm heart failure with preserved ejection fraction (HFpEF) in patients with exertional dyspnea, but current algorithms do not detect all patients. We aimed to identify additional echocardiographic markers of elevated pulmonary arterial wedge pressure during exercise (exPAWP) in patients referred for DST.

Methods and Results

We identified candidate parameters in 22 patients referred for exercise right heart catheterization with simultaneous echocardiography. Elevated exPAWP (≥25 mmHg) was present in 14 patients, and was best identified by peak septal systolic annular velocity <9.5 cm/s [exS', area under the receiver operating characteristic curve (AUC) 0.97, 95% confidence interval 0.92–1.0] and mean pulmonary artery pressure/cardiac output slope ≥3.2 mmHg/L [mPAP/CO, AUC 0.88 (0.72–1.0)]. We propose a decision tree to identify patients with elevated exPAWP. Applying this decision tree to 326 patients in an independent non-invasive DST cohort showed that patients labeled as “high probability of HFpEF” (n = 85) had reduced peak oxygen uptake [13.0 (10.7–15.1) mL/kg/min, p < 0.001 vs. intermediate/low probability], high H2FPEF score [53 (40–72) %, p < 0.001 vs. intermediate/low probability], and typical clinical characteristics. The diagnostic yield of DST increased from 11% using exercise E/e', to 62% using the decision tree.

Conclusion

In DST for suspected HFpEF, exS' was the most accurate echocardiographic parameter to identify elevated PAWP. We propose a decision tree including exS' and mPAP/CO for interpretation of DST. Application of this decision tree revealed typical HFpEF characteristics in patients labeled as high probability of HFpEF, and substantially reduced the number of inconclusive results.
Mineralogy and Pore Structure of Marine–Continental Transitional Shale: A Case Study of the Upper Carboniferous Keluke Formation in the Eastern Qaidam Basin, China
Authors: Guo Yingchun , Fang Xinxin , Wang Haifeng , Wang Na
Published: February 2022

Organic-rich shale and associated fine-grained sedimentary rocks of marine-continental transitional facies were well developed in the Upper Carboniferous Keluke Formation in the Eastern Qaidam Basin, which is expected to be a set of potential shale gas exploration and development target. Mineralogy and pore structure of marine-continental transitional shale were investigated systematically based on thin-section identification, X-ray diffraction (XRD), helium porosity test and pressure-pulse permeability measurement, scanning electron microscopy (QEMSCAN), field emission scanning electron microscopy (FESEM), and high-pressure mercury injection (MICP) and nitrogen adsorption. Thin section, XRD, and QEMSCAN data suggest that marine–continental transitional shale has complex mineral compositions, resulting in mixed rocks and mixed sequences. FE-SEM images show that interparticle and intercrystalline pores are popular in the Keluke Shales, with minor dissolution pores and microfractures. No secondary organic matter pores occur in the Keluke Shales because organic macerals are dominated by vitrinite and inertinite, where only primary pores can be found among organic matter frameworks. MICP and nitrogen adsorption indicate that pore size distributions follow a bimodal pattern and proportions of micro-scale pores and macro-scale pores increase in an order: bioclastic limestone, argillaceous bioclastic limestone, silty mudstone, argillaceous siltstone. The differences in pore structure are caused by sedimentary facies and associated mineralogy and diagenesis. This study can provide a crucial theoretical guidance for sweet spots determination and deep understanding of transitional shale gas potential.
The Accuracy and Efficiency of a Reference-Based Adaptive Selection Algorithm for Comparative Judgment
Authors: Verhavert San , Furlong Antony , Bouwer Renske
Published: February 2022

Several studies have proven that comparative judgment (CJ) is a reliable and valid assessment method for a variety of competences, expert assessment, and peer assessment, and CJ is emerging as a possible approach to help maintain standards over time. For consecutive pairs of student works (representations) assessors are asked to judge which representation is better. It has been shown that random construction of pairs leads to very inefficient assessments, requiring a lot of pairwise comparisons to reach reliable results. Some adaptive selection algorithms using information from previous comparisons were proposed to increase the efficiency of CJ. These adaptive algorithms appear however to artificially inflate the reliability of CJ results through increasing the spread of the results. The current article proposes a new adaptive selection algorithm using a previously calibrated reference set. Using a reference set should eliminate the reliability inflation. In a real assessment, using reference sets of different reliability, and in a simulation study, it is proven that this adaptive selection algorithm is more efficient without reducing the accuracy of the results and without increasing the standard deviation of the assessment results. As a consequence, a reference-based adaptive selection algorithm produces high and correct reliability values in an efficient manner.
The Impacts of Changes in Anthropogenic Emissions Over China on PM2.5 Concentrations in South Korea and Japan During 2013–2017
Authors: Xie Peifu , Liao Hong
Published: February 2022

We applied the global 3-D chemical transport model GEOS-Chem to examine the effects of changes in anthropogenic emissions over China on PM2.5 concentrations in South Korea and Japan over 2013–2017 during which the Chinese governmental “Action Plan on the Prevention and Control of Air Pollution” was implemented. The reductions in anthropogenic emissions in China alleviated PM2.5 concentrations in South Korea and Japan. The reductions in anthropogenic emissions in China alone led to reductions in annual mean PM2.5 concentrations by 13.7 (19.7%), 2.7 (7.7%), and 1.0 (7.9%) μg m−3 over 2013–2017 in eastern China, South Korea, and Japan, respectively. The reductions in anthropogenic emissions in China also changed the components of PM2.5 in South Korea and Japan. The concentrations of sulfate, ammonium, black carbon and organic carbon were simulated to decrease and those of nitrate were simulated to increase in both South Korea and Japan. With the changes in anthropogenic emissions and the changes in meteorology (BASE simulation), the proportions of sulfate, nitrate, and OC in PM2.5 in South Korea (Japan) were, respectively, 17.1, 44.4, and 15.8% (27.2, 30.5, and 20.0%) in 2013, and 14.3, 46.0, and 17.8% (23.7, 33.2, and 21.6%) in 2017. Model results shown here are helpful for understanding the temporal evolution in PM2.5 on different timescales in the downwind regions of China.
Role of Suprabasin in the Dedifferentiation of Follicular Epithelial Cell-Derived Thyroid Cancer and Identification of Related Immune Markers
Authors: Tan Hao , Wang Lidong , Liu Zhen
Published: February 2022

Background: Aberrant regulation of suprabasin (SBSN) is associated with the development of cancer and immune disorders. SBSN influences tumor cell migration, proliferation, angiogenesis, and immune resistance. In this study, we investigated the potential correlation between SBSN expression and immune infiltration in thyroid cancer.

Methods: The expression of SBSN in 80 papillary thyroid carcinoma (PTC) specimens was determined using quantitative reverse-transcription polymerase chain reaction, western blotting, and immunohistochemical staining. The expression of SBSN in 9 cases of poorly differentiated thyroid carcinoma (PDTC) and 18 cases of anaplastic thyroid carcinoma (ATC) was evaluated by immunohistochemical staining. Comprehensive bioinformatics analysis of SBSN expression was performed using The Cancer Genome Atlas and Gene Expression Omnibus datasets, and the relationship of SBSN expression with M2 macrophages and T regulatory cells (Tregs) in ATC and PTC was verified by immunohistochemical staining.

Results: Compared with those in adjacent normal tissues, the expression levels of SBSN mRNA and protein were significantly higher in PTC tissues. SBSN expression level was correlated with that of cervical lymph node metastasis in PTC patients. Immunohistochemical staining results showed statistically significant differences among high-positive expression rates of SBSN in PTC, PDTC, and ATC. Functional enrichment analysis showed that SBSN expression was associated with pathways related to cancer, cell signaling, and immune response. Furthermore, analysis of the tumor microenvironment (using CIBERSORT-ABS and xCell algorithms) showed that SBSN expression affected immune cell infiltration and the cancer immunity cycle, and immunohistochemistry confirmed a significant increase in M2 macrophage and Treg infiltration in tumor tissues with high-positive SBSN expression.

Conclusion: These findings reveal that SBSN may be involved in thyroid carcinogenesis, tumor dedifferentiation progression, and immunosuppression as an important regulator of tumor immune cell infiltration.
lncRNA Mirt1: A Critical Regulatory Factor in Chronic Intermittent Hypoxia Exaggerated Post-MI Cardiac Remodeling
Authors: Wang Xinxia , Li Zexuan , Du Yunhui , Xing Yuanyuan , Guo Yingying , Zhang Yushi , Guo Ruifeng , Gong Wei , Nie Shaoping , Wang Xiao
Published: February 2022

Chronic intermittent hypoxia (CIH) is the main feature of obstructive sleep apnea (OSA) and is known to exaggerate cardiac remodeling after myocardial infarction (MI). However, the specific contribution of CIH to overall OSA-induced pathological complications and the transcriptomic mechanisms underlying CIH-exaggerated post-MI remodeling remains unclear. In this study, we used RNA-sequencing to construct the expression profiles of cardiac mRNAs, microRNAs, and long non-coding RNAs (lncRNA) in four groups of C57BL/6J mice (Sham, CIH, MI, MI + CIH) to evaluate how CIH regulates cardiac remodeling after MI. Compared with the other three groups, the MI + CIH group exhibited 345 lncRNAs, 35 microRNAs, and 5,220 differentially expressed mRNAs. Further analysis showed that CIH led to significant changes in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed mRNAs. Co-expression network analysis identified two core lncRNAs (Mirt1 and AC125351.1) and two core microRNAs (miR-466i-5p and miR-574-5p) during the development of CIH-exaggerated post-MI remodeling, and they were verified by quantitative real-time PCR (qRT-PCR). LncRNA-mRNA correlation analysis further showed that lncRNA Mirt1 was positively correlated with Apbb1ip and Lcp2. In addition, microRNA-mRNA correlation analysis showed that microRNA miR-466i-5p was positively correlated with Snai2, Cdc27, and Ngfr. Furthermore, combining with lncRNA-mRNA and miRNA-mRNA networks, 44 RNAs were identified in the competitive endogenous RNA (ceRNA) network. Mirt1 acts as a ceRNA to bind to miR-466i-5p to further regulate the expression levels of the target gene, thereby aggravating cardiac remodeling after MI. In conclusion, our study provides a systematic perspective on the potential functions of mRNAs, microRNAs, and lncRNAs in CIH-exaggerated post-MI cardiac remodeling. Our data suggest that lncRNA Mirt1 may be the most critical regulator of MI aggravated by CIH.
LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis
Authors: Dai Wei , Zheng Ping , Luo Deqiang , Xie Qian , Liu Fen , Shao Qiang , Zhao Ning , Qian Kejian
Published: February 2022

Objectives

Sepsis is a clinical disease that is typically treated in the intensive care unit, and the complex pathophysiology under this disease has not been thoroughly understood. While ferroptosis is involved in inflammation and infection, its effect in sepsis is still unknown. The study aimed to identify ferroptosis-related genes in sepsis, providing translational potential therapeutic targets.

Methods

The dataset GSE65682 was used to download the sample source from the Gene Expression Omnibus (GEO) database. Consensus weighted gene co-expression network analysis (WGCNA) was performed to find suspected modules of sepsis. The differentially expressed genes (DEGs) most significantly associated with mortality were intersected with those altered by lipopolysaccharide (LPS) treatment and were further analyzed for the identification of main pathways of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The related pathway markers were further verified by qPCR.

Results

A total of 802 blood samples with sepsis were included for WGCNA, which identified 21 modules. Intersected with ferroptosis databases and LPS treatment groups, we identified two ferroptosis-related genes: PEBP1 and LPIN1. Only LPIN1 contributes to a poor outcome. Then, 205 DEGs were further identified according to the high or low LPIN1 expression. Among them, we constructed a gene regulatory network with several transcriptional factors using the NetworkAnalyst online tool and identified that these genes mostly correlate with inflammation and immune response. The immune infiltration analysis showed that lower expression of LPIN1 was related to macrophage infiltration and could be an independent predictor factor of the survival status in sepsis patients. Meanwhile, the multivariate Cox analysis showed that LPIN1 had a significant correlation with survival that was further verified by in vitro and in vivo experiments.

Conclusion

In conclusion, LPIN1 could become a reliable biomarker for patient survival in sepsis, which is associated with immune and inflammation status.
Physiological and Pathophysiological Roles of Metabolic Pathways for NET Formation and Other Neutrophil Functions
Authors: Stojkov Darko , Gigon Lea , Peng Shuang , Lukowski Robert , Ruth Peter , Karaulov Alexander , Rizvanov Albert , Barlev Nickolai A. , Yousefi Shida , Simon Hans-Uwe
Published: February 2022

Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs.
The Role of Long Non-Coding RNAs in the Tumor Immune Microenvironment
Authors: Guo Yingli , Xie Yajuan , Luo Yao
Published: February 2022

Tumorigenesis is a complicated process caused by successive genetic and epigenetic alterations. The past decades demonstrated that the immune system affects tumorigenesis, tumor progression, and metastasis. Although increasing immunotherapies are revealed, only a tiny proportion of them are effective. Long non-coding RNAs (lncRNAs) are a class of single-stranded RNA molecules larger than 200 nucleotides and are essential in the molecular network of oncology and immunology. Increasing researches have focused on the connection between lncRNAs and cancer immunotherapy. However, the in-depth mechanisms are still elusive. In this review, we outline the latest studies on the functions of lncRNAs in the tumor immune microenvironment. Via participating in various biological processes such as neutrophil recruitment, macrophage polarization, NK cells cytotoxicity, and T cells functions, lncRNAs regulate tumorigenesis, tumor invasion, epithelial-mesenchymal transition (EMT), and angiogenesis. In addition, we reviewed the current understanding of the relevant strategies for targeting lncRNAs. LncRNAs-based therapeutics may represent promising approaches in serving as prognostic biomarkers or potential therapeutic targets in cancer, providing ideas for future research and clinical application on cancer diagnosis and therapies.
Resilience of Coastal Lake Barriers in Poland in Light of Geological and Bathymetric Data and Hydrodynamic Simulations
Authors: Różyński Grzegorz , Cerkowniak Grzegorz R.
Published: February 2022

The paper presents a study on the insufficient resilience of three coastal lake barriers at the central part of the Polish Baltic Sea coast. Environmental qualities of those lakes belonging to the NATURA2000 network dictate efforts aimed at their conservation through the maintenance of the barriers. The use of recently elaborated high resolution geological surveys demonstrated previously underestimated severe sand scarcity and indicated high threats of enhanced erosion, breaching and overtopping of the barriers. Next, the investigation of alongshore variation of nearshore wave energy dissipation, basing on the available bathymetric records and the concept of ordinary and empirical equilibrium profiles, identified potential erosion hot spots along the barriers. Finally, the XBeach model was applied to simulate the effects of rare, heavy storms with the recurrence period of 20 years with and without climate change induced sea level rise. Overall, the results demonstrated high susceptibility of the barriers to frequent fragmentation and allowed for recommendations of protection measures minimizing interference into the natural landscapes. The novelty of the paper consists in the assessment of aftermaths of extreme events by combining recent advances in coastal geology and climate change effects.