bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare Association between Two Genetic Conditions: Turner Syndrome and Neurofibromatosis Type 1
Authors: El Qadiry R. , Danaoui K. , Nassih H. , Bourrahouat A. , Ait Sab I.
Published: April 2022

Turner’s syndrome (TS) is a sex chromosome disorder due to loss of either all or part of the X chromosome, in some or all the cells of the body. Neurofibromatosis type 1 (NF-1) is a multisystemic genetic disorder that is only rarely observed in association with Turner syndrome. Only six cases of Turner syndrome associated with NF-1 have been reported in the literature. In this study, we report the first case with TS and NF-1 in a Moroccan child. Case Report. A 16-year-old female was born of a nonconsanguineous marriage. In her family history, her mother had multiple café-au-lait spots with Lisch nodules on ophthalmologic examination. She was diagnosed with TS (karyotype: 45, X) due to short stature and characteristic features. The diagnosis of NF-1 was made according to the presence of four diagnostic criteria of the National Institute of Health Consensus Development Conference. Conclusion. Coexistence of NF-1 with TS is rare. We consider that this may be the seventh case report of TS associated with NF-1.
Evaluating the Systemic Importance of China’s Banks via Adjacency Information Entropy
Authors: Zhang Junzhi , Chen Lei
Published: April 2022

Information entropy can be utilized to assess the complexity of the Banking System and the uncertainty of association information between banks. Based on information entropy and the balance sheet data of 167 banks from 2011 to 2020, we proposed a centrality indicator based on Adjacency Information Entropy, then applied it to directed weighted and directed unweighted interbank networks to identify banks with systemically important status, and compared the results with those of traditional centrality indicators. The outcomes show that the results of centrality indicator based on Adjacency Information Entropy are more accurate than those of traditional centrality indicators in identifying banks with systemically important status in interbank networks. Six large state‐owned commercial banks, nine joint‐stock commercial banks, two policy banks, and two urban commercial banks with large assets are identified as systemically important banks based on the proposed centrality indicator, which is highly consistent with the list of systemically important banks published by the Chinese banking regulator. Among the systemically important banks, changes in systemic risk levels of joint‐stock commercial banks and urban commercial banks are more susceptible to national policies than those of large state‐owned commercial banks. The findings of this paper have certain reference significance for strengthening the supervision of banks with systemically important status in interbank networks and formulating targeted policies for regulating large commercial banks and small‐ and medium‐sized commercial banks.
Antibiofilm Potential of Alpha-Amylase from a Marine Bacterium, Pantoea agglomerans
Authors: Goel Charu , Shakir Chippu , Tesfaye Azene , Raghavanpillai Sabu Kuzhunellil , Idhayadhulla Akbar , Manilal Aseer , Woldemariam Melat , Vijayan Nayana , Shah Shabna
Published: April 2022

Bacterial biofilms are a big menace to industries and the environment and also in the health sector, accumulation of which is a major challenge. Despite intensive efforts to curb this issue, a definitive solution is yet to be achieved. Enzyme-templated disruption of the extracellular matrix of biofilm and its control and elimination are emerging as an efficient and greener strategy. The study describes the antibiofilm potential of alpha-amylase from the marine microorganism Pantoea agglomerans PCI05, against food-borne pathogens. Amylase exhibited stability in a wide pH range and retained 50% of its activity at temperatures as high as 100°C. Thermal analysis of the enzyme produced showed thermal stability, up to 130°C. From these findings, it can be envisaged that the alpha-amylase produced from P. agglomerans can be used for starch liquefaction; it was also evaluated for antibiofilm activity. Amylase from this marine bacterium was found to efficiently disrupt the preformed biofilms of food-borne pathogens such as Bacillus cereus, Serratia marcescens, Vibrio parahaemolyticus, Listeria monocytogenes, and Salmonella enterica enterica serotype Typhi based on the value of biofilm inhibitory concentrations.
Impact Response Prediction Method of Packaging Systems with a Key Component considering Different Excitations and Cushioning Materials
Authors: Xiao Heye , Xu ChiZhen , Yuan Focai , Zhang Xudong , Bai Junqiang , Zhou Jie
Published: April 2022

Nonlinear dynamic models of the packaging systems that consider different excitations and cushioning materials are proposed to analyze their impact responses in this paper. To solve the nonlinear dynamic equations of the models, Newmark method is combined with Newton-Arithmetic mean method to transfer nonlinear equations to the linear discretization equations. Then, the acceleration responses and dropping damage boundary curves (DDBCs) of different nonlinear cushioning packaging systems are calculated conveniently with initial conditions. The good agreements between the simulated and tested results prove the accuracy and effectiveness of the proposed method. Furthermore, the effects of excitations parameters on the DDBCs of the packaging systems are analyzed. It is found that the key parameter for introducing differences between simulated and measured DDBCs is inappropriate duration configuration in the acceleration pulse test.
In the Tumor Microenvironment, ETS1 Is an Oncogenic Immune Protein: An Integrative Pancancer Analysis
Authors: Wu Zixuan , Jiang Yanhui , Huang Xuyan , Cai Minjie , Yuan Kai , Huang Peidong , Wang Zuhong
Published: April 2022

Background. Previous research suggested that ETS1 (ETS proto-oncogene 1, transcription factor) could be useful for cancer immunotherapy. The processes underlying its therapeutic potential, on the other hand, have yet to be thoroughly investigated. The purpose of this study was to look into the relationship between ETS1 expression and immunity. Methods. TCGA and GEO provide raw data on 33 different cancers as well as GSE67501, GSE78220, and IMvigor210. In addition, we looked at ETS1's genetic changes, expression patterns, and survival studies. The linkages between ETS1 and TME, as well as its association with immunological processes/elements and the major histocompatibility complex, were explored to effectively understand the role of ETS1 in cancer immunotherapy. Three distinct immunotherapeutic cohorts were employed to examine the relationship between ETS1 and immunotherapeutic response. Results. ETS1 expression was shown to be high in tumor tissue. ETS1 overexpression is linked to a worse clinical outcome in individuals with overall survival. Immune cell infiltration, immunological modulators, and immunotherapeutic signs are all linked to ETS1. Overexpression of ETS1 is linked to immune-related pathways. However, no statistically significant link was found between ETS1 and immunotherapeutic response. Conclusions. ETS1 may be a reliable biomarker for tumor prognosis and a viable prospective therapeutic target for human cancer immunotherapy (e.g., KIRP, MESO, BLCA, KIRC, and THYM).
Research on the Construction and Realization of Data Pipeline in Machine Learning Regression Prediction
Authors: Zhang Hua , Zheng Guoxun , Xu Jun , Yao Xuekun
Published: April 2022

The data set used by machine learning usually contains missing value and text type data, and sometimes, it is necessary to combine the attributes in the data set. The data set must be cleaned and converted before the machine learning model can be generated. This is frequently a chain of events. The entire processing procedure will be time-consuming and inconvenient. This article examines the data pipeline and recommends that it be used to process all data. We carry out automation and use k-fold cross-validation to evaluate the performance of the model. Experiments demonstrate that it can lower the regression prediction model’s root mean square error and enhance prediction accuracy.
Analyses of Grating Lobe and Beam Fixation Problems of Low-Profile Dynamic Antenna
Authors: Liu Jibin , Xu Ming , Lin Mingtuan , Li Yangfei , Deng Bowen , Lee Yuanxin , Zhang Jihong , Liu Peiguo
Published: April 2022

Dynamic metasurface antennas (DMAs) and dynamic antenna arrays (DAAs) are emerging concepts in low-profile antenna design, providing alternative structures with lower circuit complexity and power requirements for radar and communication systems. However, dynamic antennas are prone to significant grating lobe and beam fixation problems due to their discrete amplitude and phase control. The reasons behind these issues are explored through mathematical and simulation analysis of three specific cases, and solutions are subsequently proposed and partially experimentally verified.
Correlation between Testicular Morphometric Parameters and Sperm Reserves in Ghanaian West African Dwarf Rams
Authors: Atawalna Joseph , Junior Essel Daniel Cobbinah , Nettey Nicholas , Amponsah Patrick Mensah
Published: April 2022

The current study was conducted to investigate the association between testicular morphometric parameters and sperm reserves in Ghanaian West African Dwarf rams. The intact scrotum along with testes and epididymides from twelve rams were collected immediately after slaughtering and transported to the Regional Veterinary Laboratory. The left testes and epididymides from all rams were dissected and the testes were individually weighed. The individual length, width, and volume of the testis and cauda epididymis were determined. Tissue samples were taken from testicular parenchyma, homogenized, and used to determine gonadal sperm concentration using a hemocytometer. Spermatozoa were recovered from the cauda epididymis by the incision method and used to determine the spermiogram. The weight, length, width, and volume of the testis were 63 ± 11 gram, 6.7 ± 0.44 cm, and 4.6 ± 0.40 and 74 ± 19 cm3, respectively, while the same parameters (except weight) for the cauda epididymis were 3.2 ± 0.35 cm, 1.8 ± 0.16 cm, and 5.48 ± 1.5 cm3, respectively. The sperm reserves per testis (SR), sperm reserves per gram testis (SRG), daily sperm production per testis (DSP), and daily sperm production per gram testis (DSPG) were (11,740 ± 386, 250 ± 6, 2350 ± 7.7, and 50 ± 1.0) million sperm cells, respectively. The cauda epididymal sperm reserves were 1,386 ± 456 million sperm cells, and the sperm motility (M%), morphologically normal viable cells (N%), dead sperm cells (D%), and morphologically abnormal sperm cells (A%) were 89 ± 3.2, 70.13 ± 8.0, 13.55 ± 5.05, and 16.33 ± 7.9, respectively. In conclusion, testicular morphometric parameters in Ghanaian West African Dwarf rams are highly and positively correlated (r = 0.7487–0.9354) with sperm reserves and production.
Anticancer, Antibacterial, Antioxidant, and DNA‐Binding Study of Metal‐Phenalenyl Complexes
Authors: Sen Subhadeep , Chowdhury Nilkanta , Kim Tae-Wan , Paul Mohuya , Debnath Dilip , Jeon Seob , Bagchi Angshuman , Im Jungkyun , Biswas Goutam
Published: April 2022

Phenalenyl (PLY)‐based metal complexes are a new addition to the metal complex family. Various applications of metal‐based phenalenyl complexes (metal‐PLY) have been reported, such as catalyst, quantum spin simulators, spin electronic devices, and molecular conductors, but the biological significance of metal‐PLY (metal = Co(II), Mn(III), Ni(II), Fe(III), and Al(III)) systems has yet to be explored. In this study, the anticancer properties of such complexes were investigated in ovarian cancer cells (SKOV3 and HEY A8), and the cytotoxicity was comparable to that of other platinum‐based drugs. Antibacterial activity of the metal‐PLY complexes against both gram‐negative (E. coli) and gram‐positive (S. aureus) bacteria was studied using a disk diffusion test and minimum inhibitory concentration (MIC) methods. All five metal‐PLY complexes showed significant antibacterial activity against both bacterial strains. The antioxidant properties of metal‐PLY complexes were evaluated following the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) scavenging method and were acceptable. The DNA‐binding properties of these metal‐PLY complexes were investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements, and thermal denaturation methods. Experimental evidence revealed that the complexes bind to DNA through intercalation, and the molecular docking study supported this conclusion.
Technical Diagnosis on Elite Female Discus Athletes Based on Grey Relational Analysis
Authors: Chen Dong , Ma Xuejun , Dong Jiawei
Published: April 2022

The personalized training of elite athletes is the key to the breakthrough of Chinese track and field events in the Tokyo Olympic Games. The brilliance of Chinese women’s throwing benefits from the closed-loop personalized training system. Training starts from the construction of accurate personalized technology and physical fitness model. This paper introduces the concept of champion model and puts forward a targeted technical training system based on the differentiation research of champion model. This paper mainly studies and analyzes some important technical parameters and achievements of elite female discus athletes aged 2018∼2021 by using the methods of Pearson, partial correlation and grey correlation analysis. We select from several technical parameters with significant differences, choose from several technical parameters that have significant difference, and calculate the correlation parameters and results. The results show that the influence degree of these technical parameters is as follows: torso angle of right foot touching the ground, discus release angle, discus release speed, shoulder and arm passing angle of left foot off the ground, discus moving distance of double support, center of mass moving distance of double support, and time of the second single support stage. This is different from our view that the hand speed is the most important, so the training of elite athletes should be more refined and specialized to promote the improvement of their performance. Through the application of technical diagnosis model in Chen Yang in a period of time, Chen Yang got her best result (65.14 m) in Chongqing Athletics Championship, which verified the success of the technical diagnosis model and application in this study.
The Classroom Education Model of Artificial Intelligence and Information Technology Supported by Wireless Networks
Authors: Yang Shaoqing , Huang Yan , Wang Yawen , Li Wentao
Published: April 2022

Multimodal is one of the methods of teaching or ideas formed from a different set of models and teaching content to enhance the student’s experience in their field of study. This method can be implemented in various scenarios, such as video lessons, interactive elements, and a list of questions. Teachers should have enough ideas to cover students in all the categories. The students have to listen to the courses through an online learning platform or a live session. This proposed work focuses on multimodal teaching and learning concepts combined with wireless sensor networks and AI. Additionally, the implementation of technology in classroom education is being done to handle the multimodal data. This idea is implemented with the Random Offloading Algorithm which works based on the multiagent system. This multiagent system is implemented for optimizing the user’s response delay and hence balancing the effective resource allocation of the server. The main role of this Random Offloading Algorithm in the proposed system is to focus on the online classes for the students through wireless network and to make effective response to the student’s queries. The proposed system is later compared with the existing ANN classification model. The results show that the proposed algorithm has provided 98.99% accuracy in providing better classroom education.
The Flat Plate Boundary Layer Equation under Blasius Restrictions with a Unique Solution
Authors: Jaguaribe Emerson Freitas
Published: April 2022

Even though Blasius’s flat plate boundary layer equation is considered an outstanding application of the boundary layer theory, it presents a series of inconsistencies both in its deduction and solution. This work reexamines, in detail, the fundamentals of the classical equation and the method to solve it to build correlations associated with the proposed new flat plate boundary equation and its solution. It deals with being well aware of avoiding or excluding the existing mathematical and erroneous physical considerations involved to improve the design, analysis, and solution of many practical problems in the fields of Fluid Mechanics and other scientific and technical areas. The new proposed flat plate boundary layer equation has a unique solution and satisfies Prandtl’s boundary layer concept; its inherent flow is sensitive to the transition phenomenon. In this sense, depending on the Reynolds number, it can generate perturbations that will justify the origin of the Tollmien–Schlitching waves.
Ketogenesis Attenuates KLF5-Dependent Production of CXCL12 to Overcome the Immunosuppressive Tumor Microenvironment in Colorectal Cancer
Authors: Wei Ruozheng , Zhou Yuning , Li Chang , Rychahou Piotr , Zhang Shulin , Titlow William B. , Bauman Greg , Wu Yuanyuan , Liu Jinpeng , Wang Chi , Weiss Heidi L. , Evers B. Mark , Wang Qingding
Published: April 2022

The dynamic composition of the tumor microenvironment (TME) can markedly alter the response to targeted therapies for colorectal cancer. Cancer-associated fibroblasts (CAF) are major components of TMEs that can direct and induce infiltration of immunosuppressive cells through secreted cytokines such as CXCL12. Ketogenic diets (KD) can inhibit tumor growth and enhance the anticancer effects of immune checkpoint blockade. However, the role of ketogenesis on the immunosuppressive TME is not known. Here, we show that decreased ketogenesis is a signature of colorectal cancer and that an increase in ketogenesis using a KD decreases CXCL12 production in tumors, serum, liver, and lungs. Moreover, increasing ketogenesis by overexpression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) or treatment with the ketone body β-hydroxybutyrate markedly decreased expression of KLF5, which binds the CXCL12 promoter and induces CXCL12 expression in CAFs. KD decreased intratumoral accumulation of immunosuppressive cells, increased infiltration of natural killer and cytotoxic T cells, and enhanced the anticancer effects of PD-1 blockade in murine-derived colorectal cancer. Furthermore, increasing ketogenesis inhibited colorectal cancer migration, invasion, and metastasis in vitro and in vivo. Overall, ketogenesis is downregulated in the colorectal cancer TME, and increased ketogenesis represses KLF5-dependent CXCL12 expression to improve the immunosuppressive TME, which leads to the enhanced efficacy of immunotherapy and reduced metastasis. Importantly, this work demonstrates that downregulation of de novo ketogenesis in the TME is a critical step in colorectal cancer progression.

Significance:

This study identifies ketogenesis as a critical regulator of the tumor microenvironment in colorectal cancer and suggests the potential for ketogenic diets as a metabolic strategy to overcome immunosuppression and prolong survival.

See related commentary by Montrose and Galluzzi, p. 1464
Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon
Authors: Matas Julia , Kohrn Brendan , Fredrickson Jeanne , Carter Kelly , Yu Ming , Wang Ting , Gui Xianyong , Soussi Thierry , Moreno Victor , Grady William M. , Peinado Miguel A. , Risques Rosa Ana
Published: April 2022

Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without colorectal cancer. This testing platform revealed that normal colon from patients with and without colorectal cancer carries mutations in common colorectal cancer genes, but these mutations are more abundant in patients with cancer. Oncogenic KRAS mutations were observed in the normal colon of about one third of patients with colorectal cancer but in none of the patients without colorectal cancer. Patients with colorectal cancer also carried more TP53 mutations than patients without cancer and these mutations were more pathogenic and formed larger clones, especially in patients with early-onset colorectal cancer. Most mutations in the normal colon were different from the driver mutations in tumors, suggesting that the occurrence of independent clones with pathogenic KRAS and TP53 mutations is a common event in the colon of individuals who develop colorectal cancer. These results indicate that somatic evolution contributes to clonal expansions in the normal colon and that this process is enhanced in individuals with cancer, particularly in those with early-onset colorectal cancer.

Significance:

This work suggests prevalent somatic evolution in the normal colon of patients with colorectal cancer, highlighting the potential of using ultrasensitive gene sequencing to predict disease risk.
The Continuing Search for Causality between Epithelial-to-Mesenchymal Transition and the Metastatic Fitness of Carcinoma Cells
Authors: LeBleu Valerie S. , Thiery Jean Paul
Published: April 2022

The epithelial-to-mesenchymal transition (EMT) is an epithelial plasticity program that is associated with embryonic development and organogenesis, and which resurfaces to a certain extent following epithelial injury caused by inflammation, fibrosis, and carcinoma progression. Carcinoma cell EMT plasticity programs superimposed on inherent genetic defects have been implicated as important for metastatic dissemination and secondary tumor formation. A careful review of data-driven facts suggests that a causal relationship between any degree of EMT program and metastasis continues to be elusive, and the steps of metastasis likely involve other mechanisms influenced by the carcinoma cell genotype and the tumor microenvironment.
Procjena funkcionalnog statusa u bolesnika s teškom aortalnom stenozom nakon transkateterske implantacije aortalnog zaliska
Authors: Stanišić Pavica , Kvaternik Morena , Ivanišević Kata
Published: April 2022

Uvod: Aortalna stenoza najčešća je valvularna bolest kod osoba starijih od 65 godina. Bolesnici koji razviju teški stupanj bolesti imaju izražene simptome pri najmanjem naporu te im je smanjen funkcionalni status. Budući da lijekovi još uvijek daju slabe rezultate u liječenju, zamjena aortnog zaliska najvažniji je korak u liječenju simptomatskih bolesnika.
Cilj: Cilj je istraživanja procijeniti funkcionalni status bolesnika prije i nakon primjene TAVI-ja prema NYHA klasifikaciji.
Metode: Istraživanje je retrospektivno i provedeno je na 60 pacijenata koji su liječeni u KBC-u Rijeka u periodu od 1. 1. 2016. do 1. 1. 2020. godine zbog teške aortalne stenoze za koji je Tim za strukturalne bolesti srca procijenio potrebu za TAVI zahvatom. Funkcionalni status bolesnika procijenjen je pomoću ljestvice za procjenu funkcionalnog statusa (NYHA klasifikacija) prije i poslije zahvata, kao i ehokardiografski nalaz svih bolesnika koji su obuhvaćeni istraživanjem. Podaci su obrađeni pomoću deskriptivne i inferencijalne statistike.
Rezultati: Od ukupnog broja bolesnika, njih 60 (100 %), sudjelovala je 31 žena (52 %) i 29 muškaraca (48 %) prosječne dobi za muškarce 78,1 ± 7,3 te za žene 80,55 ± 4,43 godina. Ispitanici su prije zahvata imali razinu NYHA klasifikacije 2 – 4, dok je nakon zahvata razina NYHA klasifikacije prva ejekcijska frakcija prije TAVI zahvata kod muškaraca iznosila 45 % – 60 %, nakon zahvata iznosila je 47,5 % – 60 %, a kod žena ejekcijska frakcija prije zahvata iznosila je 50 % – 60 %, a nakon zahvata 55 % – 60 %.
Zaključak: Bolesnici s teškom aortalnom stenozom liječeni u Kliničkom bolničkom centru Rijeka nakon primjene TAVI zahvata imaju, neovisno o spolu i dobi, poboljšani funkcionalni status prema NYHA klasifikaciji.
Jesu li medicinske sestre dovoljno usmjerene prema pacijentu kao subjektu skrbi?
Authors: Domitrović Ivan
Published: April 2022

Pacijent bi trebao biti u centru sestrinskog promišljanja. Usprkos tome, medicinske sestre uslijed usmjerenosti na razne zadatke često potisnu primarni interes prema čovjeku kao osobi i uvažavanju holističkih elemenata sestrinske skrbi.
Povijesno gledano, sestrinstvo je nastalo na temeljima skrbi za drugoga, dok iz današnje perspektive uočavamo sve veću usmjerenost na izvršavanje medicinsko-tehničkih i administrativnih zadataka. Višedimenzionalan pristup u radu trebao bi biti standard sestrinske prakse u kojoj će pacijent u procesu zdravstvene skrbi moći sudjelovati u izboru postupka liječenja te u izvođenju zadataka usmjerenih prema njegovoj dobrobiti.
U suvremenim okolnostima zdravstvene skrbi u kojima se bolesnika često ne percipira kao partnera u procesu zdravstvene skrbi, nego ga se tretira kao objekt rada, ova je tema ponovno aktualna. Objektiviziranjem pacijent postaje podložan diskriminaciji, rutinizaciji i psihološkom napuštanju za vrijeme hospitalizacije kad prevladava egzistencijalna patnja i „totalna bol“. Nasuprot takvom redukcionističkom pristupu, poštivanjem norme dobre kliničke prakse, etičkih principa, pacijentovih prava i vlastitom unutarnjom motivacijom, medicinska sestra stvara čvrsto tlo za razvoj pacijento-centričnog odnosa i poštivanja oboljelog kao subjekta u procesu rada. Stoga je važno stalno iznova poticati medicinske sestre na cjeloživotnu edukaciju i samorazvoj kako bi novim znanjima i iskustvima doprinijele pacijentovoj najvećoj mogućoj dobrobiti.
A TCR mimic CAR T cell specific for NDC80 is broadly reactive with solid tumors and hematologic malignancies
Authors: Klatt Martin G. , Dao Tao , Yang Zhiyuan , Liu Jianying , Mun Sung Soo , Dacek Megan M. , Luo Hanzhi , Gardner Thomas J. , Bourne Christopher , Peraro Leila , Aretz Zita E. H. , Korontsvit Tanya , Lau Michael , Kharas Michael G. , Liu Cheng , Scheinberg David A.
Published: April 2022

Target identification for chimeric antigen receptor (CAR) T-cell therapies remains challenging due to the limited repertoire of tumor-specific surface proteins. Intracellular proteins presented in the context of cell surface HLA provide a wide pool of potential antigens targetable through T-cell receptor mimic antibodies. Mass spectrometry (MS) of HLA ligands from 8 hematologic and nonhematologic cancer cell lines identified a shared, non-immunogenic, HLA-A*02–restricted ligand (ALNEQIARL) derived from the kinetochore-associated NDC80 gene. CAR T cells directed against the ALNEQIARL:HLA-A*02 complex exhibited high sensitivity and specificity for recognition and killing of multiple cancer types, especially those of hematologic origin, and were efficacious in mouse models against a human leukemia and a solid tumor. In contrast, no toxicities toward resting or activated healthy leukocytes as well as hematopoietic stem cells were observed. This shows how MS can inform the design of broadly reactive therapeutic T-cell receptor mimic CAR T-cell therapies that can target multiple cancer types currently not druggable by small molecules, conventional CAR T cells, T cells, or antibodies.
LPInsider: a webserver for lncRNA–protein interaction extraction from the literature
Authors: Li Ying , Wei Lizheng , Wang Cankun , Zhao Jianing , Han Siyu , Zhang Yu , Du Wei
Published: April 2022

Background

Long non-coding RNA (LncRNA) plays important roles in physiological and pathological processes. Identifying LncRNA–protein interactions (LPIs) is essential to understand the molecular mechanism and infer the functions of lncRNAs. With the overwhelming size of the biomedical literature, extracting LPIs directly from the biomedical literature is essential, promising and challenging. However, there is no webserver of LPIs relationship extraction from literature.

Results

LPInsider is developed as the first webserver for extracting LPIs from biomedical literature texts based on multiple text features (semantic word vectors, syntactic structure vectors, distance vectors, and part of speech vectors) and logistic regression. LPInsider allows researchers to extract LPIs by uploading PMID, PMCID, PMID List, or biomedical text. A manually filtered and highly reliable LPI corpus is integrated in LPInsider. The performance of LPInsider is optimal by comprehensive experiment on different combinations of different feature and machine learning models.

Conclusions

LPInsider is an efficient analytical tool for LPIs that helps researchers to enhance their comprehension of lncRNAs from text mining, and also saving their time. In addition, LPInsider is freely accessible from http://www.csbg-jlu.info/LPInsider/ with no login requirement. The source code and LPIs corpus can be downloaded from https://github.com/qiufengdiewu/LPInsider.
Deep clustering of small molecules at large-scale via variational autoencoder embedding and K-means
Authors: Hadipour Hamid , Liu Chengyou , Davis Rebecca , Cardona Silvia T. , Hu Pingzhao
Published: April 2022

Background

Converting molecules into computer-interpretable features with rich molecular information is a core problem of data-driven machine learning applications in chemical and drug-related tasks. Generally speaking, there are global and local features to represent a given molecule. As most algorithms have been developed based on one type of feature, a remaining bottleneck is to combine both feature sets for advanced molecule-based machine learning analysis. Here, we explored a novel analytical framework to make embeddings of the molecular features and apply them in the clustering of a large number of small molecules.

Results

In this novel framework, we first introduced a principal component analysis method encoding the molecule-specific atom and bond information. We then used a variational autoencoder (AE)-based method to make embeddings of the global chemical properties and the local atom and bond features. Next, using the embeddings from the encoded local and global features, we implemented and compared several unsupervised clustering algorithms to group the molecule-specific embeddings. The number of clusters was treated as a hyper-parameter and determined by the Silhouette method. Finally, we evaluated the corresponding results using three internal indices. Applying the analysis framework to a large chemical library of more than 47,000 molecules, we successfully identified 50 molecular clusters using the K-means method with 32 embeddings based on the AE method. We visualized the clustering result via t-SNE for the overall distribution of molecules and the similarity maps for the structural analysis of randomly selected cluster-specific molecules.

Conclusions

This study developed a novel analytical framework that comprises a feature engineering scheme for molecule-specific atomic and bonding features and a deep learning-based embedding strategy for different molecular features. By applying the identified embeddings, we show their usefulness for clustering a large molecule dataset. Our novel analytic algorithms can be applied to any virtual library of chemical compounds with diverse molecular structures. Hence, these tools have the potential of optimizing drug discovery, as they can decrease the number of compounds to be screened in any drug screening campaign.
Construction of a high-density genetic map and identification of QTLs related to agronomic and physiological traits in an interspecific (Gossypium hirsutum × Gossypium barbadense) F2 population
Authors: Si Zhanfeng , Jin Shangkun , Chen Jiedan , Wang Sen , Fang Lei , Zhu Xiefei , Zhang Tianzhen , Hu Yan
Published: April 2022

Background

Advances in genome sequencing technology, particularly restriction-site associated DNA sequence (RAD-seq) and whole-genome resequencing, have greatly aided the construction of cotton interspecific genetic maps based on single nucleotide polymorphism (SNPs), Indels, and other types of markers. High-density genetic maps can improve accuracy of quantitative trait locus (QTL) mapping, narrow down location intervals, and facilitate identification of the candidate genes.

Result

In this study, 249 individuals from an interspecific F2 population (TM-1 and Hai7124) were re-sequenced, yielding 6303 high-confidence bin markers spanning 5057.13 cM across 26 cotton chromosomes. A total of 3380 recombination hot regions RHRs were identified which unevenly distributed on the 26 chromosomes. Based on this map, 112 QTLs relating to agronomic and physiological traits from seedling to boll opening stage were identified, including 15 loci associated with 14 traits that contained genes harboring nonsynonymous SNPs. We analyzed the sequence and expression of these ten candidate genes and discovered that GhRHD3 (GH_D10G0500) may affect fiber yield while GhGPAT6 (GH_D04G1426) may affect photosynthesis efficiency.

Conclusion

Our research illustrates the efficiency of constructing a genetic map using binmap and QTL mapping on the basis of a certain size of the early-generation population. High-density genetic map features high recombination exchanges in number and distribution. The QTLs and the candidate genes identified based on this high-density genetic map may provide important gene resources for the genetic improvement of cotton.
CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study
Authors: Fransén Karin , Pettersson Carolina , Hurtig-Wennlöf Anita
Published: April 2022

Background

The C-reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide polymorphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardiovascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels or early signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influence of five genetic variants on both plasma CRP levels and carotid intima-media thickness (cIMT) values, including aspects on estrogen containing contraceptive use in females.

Methods

Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serum levels in 780 Swedish young, self-reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASE v 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self-reported.

Results

Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, and rs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effect of genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non-carriers. This was specifically pronounced in the estrogen-using group (p < 0.001), and they had also higher cIMT (p = 0.002) than non-carriers but with a small cIMT difference between the haplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using group was observed (r = 0.194; p = 0.026).

Conclusions

Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels. Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and a marginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage could be involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and the observed difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies may shed further light on the role of more long-term estrogen use and early atherosclerosis.
Health-related quality of life in Italian children and adolescents with congenital heart diseases
Authors: Amodeo Giulia , Ragni Benedetta , Calcagni Giulio , Piga Simone , Giannico Salvatore , Yammine Marie Laure , Drago Fabrizio , Ciofi degli Atti Marta Luisa , Rossi Angela , De Stasio Simona , Grimaldi Capitello Teresa
Published: April 2022

Background

Congenital heart disease (CHD) is the most common congenital anomaly at birth, affecting approximately 1% of live births. In recent decades great medical and surgical advances have significantly increased life expectancy, shifting healthcare professionals' and researchers’ interests in patients' Quality of Life (QoL). The main aims of our study were to evaluate generic and condition-specific QoL in a group of Italian children and adolescents with CHD and their parents and examine the level of agreement and directional disagreement between child/adolescent and parents reports on generic and condition-specific QoL.

Methods

A cross-sectional study was designed with CHD children and adolescents and their parents referred to the Cardiology Department of “Bambino Gesù” Children’s Hospital. The PedsQL scale was used, including generic (PedsQL 4.0) and cardiac-specific modules (PedsQL 3.0) were administered to patients and caregivers. A Kruskal–Wallis test was used to compare generic and cardiac module scores between patients with different ages, CHD diagnoses, and between patients who underwent surgery interventions and/or are currently taking cardiac medications.

Results

498 families were enrolled in this study. On average, patients reported a good level of generic and condition-specific QoL, as well as their mothers and fathers. Children aged between 5–7 years old reported lower generic and cardiac-specific total QoL levels than children aged 8–12 years and adolescents (13–18 years). With regard to the agreement, patient-parent agreement on condition-specific QoL ranged from 25 to 75% while on generic QoL, it ranged from 19 to 76%. The highest percentage of disagreement between parents and children was found in patients aged 5–7 years old, both for condition-specific and generic QoL rates.

Conclusions

Our study contributed to the growing body of knowledge on QoL in CHD, emphasizing the need for these families to receive support from multidisciplinary standardized care, including psychological consultations and support.
Impact of the inspiratory oxygen fraction on the cardiac output during jugulo-femoral venoarterial extracorporeal membrane oxygenation in the rat
Authors: Edinger Fabian , Schneck Emmanuel , Schulte Charlotte , Schmidt Goetz , Gehron Johannes , Sander Michael , Koch Christian
Published: April 2022

Background

Venoarterial extracorporeal membrane oxygenation (V-A ECMO) with femoral access has gained wide acceptance in the treatment of critically ill patients. Since the patient´s cardiac output (CO) can compete with the retrograde aortic ECMO-flow, the aim of this study was to examine the impact of the inspiratory oxygen fraction on the cardiac function during V-A ECMO therapy.

Methods

Eighteen male Lewis rats (350–400 g) received V-A ECMO therapy. The inspiratory oxygen fraction on the ventilator was randomly set to 0.5 (group A), 0.21 (group B), or 0 in order to simulate apnea (group C), respectively. Each group consisted of six animals. Arterial blood pressure, central venous saturation (ScvO2), CO, stroke volume, left ventricular ejection fraction (LVEF), end diastolic volume, and pressure were measured. Cardiac injury was determined by analyzing the amount of lactate dehydrogenase (LDH).

Results

During anoxic ventilation the systolic, mean and diastolic arterial pressure, CO, stroke volume, LVEF and ScvO2 were significantly impaired compared to group A and B. The course of LDH values revealed no significant differences between the groups.

Conclusion

Anoxic ventilation during V-A ECMO with femoral cannulation leads to cardiogenic shock in rats. Therefore, awake V-A ECMO patients might be at risk for hypoxia-induced complications.
MicroRNA profile of circulating CD4+ T cells in aged patients with atherosclerosis obliterans
Authors: Wang Siwen , Jiang Suiting , Feng Ruijia , Liu Jiawei , Liu Longshan , Cui Jin , Shi Yi , Ning Junjie , Jia Benyuan , Hu Zuojun , Wang Shenming
Published: April 2022

Background

To evaluate the specificity of the expression patterns of microRNAs (miRNAs) in circulating CD4+ T cells in aged patients with atherosclerosis obliterans (ASO).

Methods

A comprehensive miRNA expression study was conducted using a miRNA microarray of CD4+ T cells isolated from peripheral blood mononuclear cells (PBMCs) of 33 patients with ASO and 24 healthy donors. A t test was used for statistical analysis, and the average linkage method was used for hierarchical clustering. The results were validated by qRT–PCR. Putative targeted pathways associated with validated miRNAs were predicted with the online software DIANA miRPath.

Results

We identified 44 miRNAs based on a cutoff value of a 1.3-fold change in expression between the two groups, with 18 miRNAs showing a false discovery rate (FDR) p value < 0.05. The qRT–PCR analysis validated differences in 12 miRNAs, and 6 miRNAs were proven to be differentially expressed among three age groups (age: 35–55 years; 56–75 years; 76–95 years): the miRNAs miR-21 (p: 0.0008; 0.0009; 0.0022), miR-29b (p: 0.453; < 0.0001; < 0.0001), and miR-374b (p: < 0.0001; < 0.0001; 0.2493) showed upregulated expression in patients with ASO, while miR-142-3p (p: < 0.0001; < 0.0001; < 0.0001), miR-142-5p (p: < 0.0001; < 0.0001; < 0.0001), and miR-150 (p: < 0.0001; < 0.0001; 0.0001) showed downregulated expression in patients with ASO. The validated miRNAs participated in CD4+ T cell activation, proliferation, and migration pathways.

Conclusions

Circulating CD4+ T cells in aged patients with ASO may show a distinct molecular signature. This is the first time that a distinctive, validated miRNA profile from circulating CD4+ T cells in atherosclerosis has been presented. This miRNA signature may be used to help elucidate the underlying mechanism of atherosclerosis. Further clinical studies and in-depth reports will contribute to identifying predictive and therapeutic targets in these patients with atherosclerosis.
External validation of a new predictive model for falls among inpatients using the official Japanese ADL scale, Bedriddenness ranks: a double-centered prospective cohort study
Authors: Tago Masaki , Katsuki Naoko E. , Nakatani Eiji , Tokushima Midori , Dogomori Akiko , Mori Kazumi , Yamashita Shun , Oda Yoshimasa , Yamashita Shu-ichi
Published: April 2022

Background

Several reliable predictive models for falls have been reported, but are too complicated and time-consuming to evaluate. We recently developed a new predictive model using just eight easily-available parameters including the official Japanese activities of daily living scale, Bedriddenness ranks, from the Ministry of Health, Labour and Welfare. This model has not yet been prospectively validated. This study aims to prospectively validate our new predictive model for falls among inpatients admitted to two different hospitals.

Methods

A double-centered prospective cohort study was performed from October 1, 2018, to September 30, 2019 in an acute care hospital and a chronic care hospital. We analyzed data from all adult inpatients, for whom all data required by the predictive model were evaluated and recorded. The eight items required by the predictive model were age, gender, emergency admission, department of admission, use of hypnotic medications, previous falls, independence of eating, and Bedriddenness ranks. The main outcome is in-hospital falls among adult inpatients, and the model was assessed by area under the curve.

Results

A total of 3,551 adult participants were available, who experienced 125 falls (3.5%). The median age (interquartile range) was 78 (66–87) years, 1,701 (47.9%) were men, and the incidence of falls was 2.25 per 1,000 patient-days and 2.06 per 1,000 occupied bed days. The area under the curve of the model was 0.793 (95% confidence interval: 0.761–0.825). The cutoff value was set as − 2.18, making the specificity 90% with the positive predictive value and negative predictive value at 11.4% and 97%.

Conclusions

This double-centered prospective cohort external validation study showed that the new predictive model had excellent validity for falls among inpatients. This reliable and easy-to-use model is therefore recommended for prediction of falls among inpatients, to improve preventive interventions.

Trial registration

UMIN000040103(2020/04/08)
Preoperative clinical-radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using $$^{18}$$F-FDG PET/CT
Authors: Wang Yutao , Luo Shuying , Jin Gehui , Fu Randi , Yu Zhongfei , Zhang Jian
Published: April 2022

Purpose

To develop a clinical-radiomics nomogram by incorporating radiomics score and clinical predictors for preoperative prediction of microvascular invasion in hepatocellular carcinoma.

Methods

A total of 97 HCC patients were retrospectively enrolled from Shanghai Universal Medical Imaging Diagnostic Center and Changhai Hospital Affiliated to the Second Military Medical University. 909 CT and 909 PET slicers from 97 HCC patients were divided into a training cohort (N = 637) and a validation cohort (N = 272). Radiomics features were extracted from each CT or PET slicer, and features selection was performed with least absolute shrinkage and selection operator regression and radiomics score was also generated. The clinical-radiomics nomogram was established by integrating radiomics score and clinical predictors, and the performance of the models were evaluated from its discrimination ability, calibration ability, and clinical usefulness.

Results

The radiomics score consisted of 45 selected features, and age, the ratio of maximum to minimum tumor diameter, and $$^{18}$$

18

F-FDG uptake status were independent predictors of microvascular invasion. The clinical-radiomics nomogram showed better performance for MVI detection (0.890 [0.854, 0.927]) than the clinical nomogram (0.849 [0.804, 0.893]) ($$p<0.05$$

p
<
0.05

). Both nomograms showed good calibration and the clinical-radiomics nomogram’s clinical practicability outperformed the clinical nomogram.

Conclusions

With the combination of radiomics score and clinical predictors, the clinical-radiomics nomogram can significantly improve the predictive efficacy of microvascular invasion in hepatocellular carcinoma ($$p<0.05$$

p
<
0.05

) compared with clinical nomogram.